DetailsCategory: DNA RNA and CellsPublished on Friday, 20 August 2021 17:24Hits: 287

10 of 14 Patients in FT596 Single-Dose Escalation Cohorts 2 and 3 Achieved Objective Response; 7 Patients Achieved Complete Response, including 2 of 3 Patients Treated with FT596 in Combination with Rituximab Following Autologous CD19 CAR T-cell Therapy

8 of 11 Patients in FT516 Multi-Dose Escalation Cohorts 2 and 3 Achieved Objective Response, including 6 Patients that Achieved Complete Response; 5 of 8 Responders Continue in Ongoing Response at Median Time of 5.2 Months

FT596 and FT516 Treatment Regimens were Well-tolerated; No Dose-limiting Toxicities, and No Adverse Events of Any Grade of ICANS or GVHD, were Observed; Two Low-grade Adverse Events of CRS were Reported in FT596 Single-Dose Escalation Cohorts 1 and 2

SAN DIEGO, CA, USA I August 19, 2021 I Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, today highlighted positive interim clinical data from the Companys FT516 and FT596 programs for patients with relapsed / refractory B-cell lymphoma. FT516 is the Companys universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The Companys FT596 program incorporates both the hnCD16 Fc receptor and a chimeric antigen receptor (CAR) targeting CD19, which is designed to enable multi-antigen targeting of tumor cells, as well as an IL-15 receptor fusion (IL-15RF) to enhance NK cell activity and survival.

We are very pleased with the interim safety, response rates, and durability of responses observed in our ongoing clinical studies of FT516 and FT596 for the treatment of patients with relapsed / refractory B-cell lymphomas. These data continue to demonstrate that our off-the-shelf, iPSC-derived NK cell product candidates can uniquely deliver substantial therapeutic benefit and expand patient access to cell-based cancer immunotherapies, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. At this time, we are initiating multiple indication-specific, dose-expansion cohorts to broadly assess FT516 in combination with CD20-targeted monoclonal antibody regimens, including in patients that have experienced disease progression following autologous CD19-targeted CAR T-cell therapy. In addition, early clinical data with the single-dose FT596 treatment schedule have shown robust 30-day response rates and we look forward to further assessing both single-dose and multi-dose treatment regimens to validate its potential best-in-class therapeutic profile.

FT596 ProgramThe ongoing clinical trial in relapsed / refractory B-cell lymphoma is assessing a single dose of FT596 as monotherapy (Monotherapy Arm) and in combination with a single dose of rituximab (375 mg/m2) (Combination Arm) following three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine). As of the data cutoff date of June 25, 2021, 10 patients in the Monotherapy Arm and 10 patients in the Combination Arm were evaluable for assessment of safety and efficacy in the first, second, and third dose cohorts of 30 million cells (n=3 each), 90 million cells (n=4 each), and 300 million cells (n=3 each), respectively (see Table 1). Patients had received a median of four prior lines of therapy and a median of 2.5 prior lines containing CD20-targeted therapy. Of the 20 patients, 12 patients (60%) had aggressive B-cell lymphoma, 10 patients (50%) were refractory to most recent prior therapy, and seven patients (35%) were previously treated with autologous CD19-targeted CAR T-cell therapy.

In the second and third single-dose cohorts of the Monotherapy and Combination Arms comprising a total of 14 patients, 10 of 14 patients (71%) achieved an objective response, including seven patients (50%) that achieved a complete response (CR), as assessed by PET-CT scan per Lugano 2014 criteria on Day 29 following FT596 dosing. Eight of 10 patients (80%) that had not previously received CD19-targeted CAR T-cell therapy achieved an objective response, including five patients (50%) that achieved CR. Two of four patients (50%) that had previously received CD19-targeted CAR T-cell therapy, both of whom were treated in the Combination Arm, achieved a CR. In the first single-dose cohorts of the Monotherapy and Combination Arms comprising a total of six patients, only one patient achieved an objective response, suggesting dose-response treatment effects for FT596. The ongoing dose-escalation study of FT596 is currently enrolling patients in the fourth single-dose cohort of 900 million cells in each arm.

The FT596 treatment regimens were well tolerated. No dose-limiting toxicities, and no treatment-emergent adverse events (TEAEs) of any grade of immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD) were observed. Two low-grade adverse events (one Grade 1, one Grade 2) of cytokine release syndrome (CRS) were reported, both of which occurred concurrently with other confounding clinical events and resolved on the same day of onset.

FT596 Patient Case StudiesThe multi-antigen targeting functionality of FT596 is designed to uniquely address tumor heterogeneity and overcome antigen escape, and has the potential to drive responses in patients that might not effectively be treated with single-antigen targeted modalities, such as monoclonal antibodies, bispecific engagers and CAR T-cell therapies. The following are two case studies from the clinical trial:

Re-treatment with Second FT596 CycleThe FT596 protocol currently allows for the re-treatment of eligible patients with a second, single-dose cycle subject to consent of the U.S. Food and Drug Administration (FDA). All requests by the Company for re-treatment were approved by the FDA. Of note, based on review of data submitted to date to the FDA, the Company is amending its FT596 clinical protocol at the FDAs recommendation to allow for re-treatment with a second FT596 cycle without requiring the agencys consent.

In second and third single-dose cohorts of the Monotherapy and Combination Arms as of the data cutoff date, four patients with CR at the end of the first single-dose cycle were re-treated, all of whom remained in CR following disease assessment at the end of the second cycle, and an additional four patients were re-treated and had not yet been assessed for response. The second, single-dose FT596 cycle was well tolerated, and no events of any grade of CRS, ICANS, or GVHD were observed.

FT516 ProgramThe clinical trial in relapsed / refractory B-cell lymphoma is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine), a single dose of rituximab (375 mg/m2), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting. Dose escalation is currently ongoing in the fourth multi-dose cohort of 900 million cells per dose.

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting held in June, the Company highlighted positive interim clinical data for 11 patients treated in the second and third multi-dose cohorts of 90 million cells per dose (n=4) and 300 million cells per dose (n=7). Patients had received a median of three prior lines of therapy and a median of two prior lines containing CD20-targeted therapy. Of the eleven patients, eight patients had aggressive B-cell lymphoma, five patients were refractory to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy. No dose-limiting toxicities, and no FT516-related serious adverse events or FT516-related Grade 3 or greater adverse events, were observed. The FT516 treatment regimen was well tolerated, and no TEAEs of any grade of CRS, ICANS, or GVHD were reported.

Ongoing Response AssessmentOf the 11 patients treated in the second and third multi-dose cohorts, eight patients (73%) achieved an objective response, including six patients (55%) who achieved CR, as assessed by PET-CT scan per Lugano 2014 criteria on Day 29 following the second FT516 treatment cycle. Notably, two of four patients (50%) previously treated with autologous CD19 CAR-T cell therapy achieved CR. At three months following first infusion, all eight responders maintained their response without further therapeutic intervention (3-Month Rate of 73% OR and 55% CR). As of the data cutoff date of July 7, 2021:

FT516 Patient Case StudyThe ASCO presentation featured a case study of a 36-year old male with triple-hit, high-grade B-cell lymphoma with rearrangements of MYC, BCL2, and BCL6 genes. The patient was refractory to all prior lines of therapy with the exception of autologous CD19 CAR T-cell therapy, for which a complete response of two months duration was achieved. The patient was most recently refractory to an investigational CD20-targeted T-cell engager and presented with bulky lymphadenopathy with the largest lesion measuring approximately 10 centimeters. The first FT516 treatment cycle resulted in a complete response with resolution of all metabolically active disease and 85% reduction in the size of target lesions. The patient received a second FT516 treatment cycle, after which the response assessment continued to show complete response. As of the data cutoff date of July 7, 2021, the patients most recent assessment at 4.9 months showed MRD negativity, confirming a profound CR.

Today's WebcastThe Company will host a live audio webcast today, Thursday, August 19, 2021 at 4:30 p.m. ET to review interim clinical data for the Companys FT516 and FT596 off-the-shelf, iPSC-derived NK cell programs. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company's website at http://www.fatetherapeutics.com. The archived webcast will be available on the Company's website beginning approximately two hours after the event.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About FT596FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors enhances cytotoxic activity, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab, and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

SOURCE: Fate Therapeutics

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Fate Therapeutics Announces Positive Interim Clinical Data from its FT596 and FT516 Off-the-shelf, iPSC-derived NK Cell Programs for B-cell Lymphoma |...

Because Animals CEO Shannon Falconer

Courtesy: Because, Animals

The CEO of pet food start-up Because Animals, Shannon Falconer, doesn't eat meat and hasn't for years, but the former Stanford microbiologist and longtime animal rescue volunteer says she never denied her pets the meat they craved. After all, cats are carnivores and dogs are omnivores in the wild.

Falconer and Because Animals co-founder Joshua Errett (also an experienced animal rescuer) have been working to make pet foods that cater to cats' and dogs' "ancestral diet," but do not require slaughtering animals, or raising them in an industrial setting.

This week, the start-up is bringing its Harmless Hunt Cultured Mouse Cat Treats, their first clean meat product, to SuperZoo one of the biggest trade shows in the pet food industry.

The treats are made with mouse tissue grown from stem cells in a food-grade bioreactor on a vegan medium, Falconer explained. No mice were killed to make the treats, but scientists had to take cells from the ears of donor mice to get started. The process involved putting a mouse under a mild anesthetic while their ear was pierced.

Two years later, the donor mice are doing well, Falconer says. Employees of Because Animals adopted all three of them, and they live in a rather plush mouse house.

Joshua Errett, COO and co-founder of Because Animals.

Courtesy: Because, Animals.

Most companies involved in the nascent clean meat industry are focused on producing food for humans.

These include: the Dutch start-up Mosa Meat which garnered buzz with the world's first cultured beef burger in 2013; Israeli venture Aleph Farms, which is making "slaughter-free steaks"; Upside Foods in California, which is making cultured chicken and duck; and Bluu Biosciences developers of cultured seafoods from fish cells, among many others.

As CNBC previously reported, the market for alternative meat -- including clean meat -- is expected to reach $140 billion over the next decade, capturing about 10% of the $1.4 trillion global meat industry.

Clean meat is not without its critics. Nobody has managed to scale lab-grown meat production to levels that show promise for feeding the world quite yet.

Additionally, University of Oxford researchers have noted, "It is not yet clear what the emissions footprints of real cultured production systems will look like." At the same time, animal tech advances promise to make the traditional meat industry healthier, and more sustainable.

Still, venture investors have jumped at the opportunity to disrupt the traditional industry, and hopefully, lessen the negative environmental impacts of global meat consumption. According to a PitchBook analysis, 66 clean meat start-ups have raised $1.77 billion in venture funding from 382 distinct investors already.

For its part, Because Animals has raised $6.7 million to date, from investors including SOSV,Draper Associates and Orkla. SOSV is one of the most active investors in this space, with at least 10 clean meat companies in its portfolio as of July 2021.

A general partner with SOSV, Bill Liao, said Because Animals may cut a faster path to mass production than other clean meat companies.

For one, Because Animals isn't making tiny mouse meat steaks -- it just needs to produce enough cultured mouse tissue to give its pet food a flavor profile cats and dogs will love. (The company's new treats do include other ingredients like cultured yeasts and pumpkin, Falconer told CNBC.)

He added, "One of the biggest challenges in cellular agriculture is sustainable, inexpensive media." Because Animals has developed that very thing and it's vegan.

Many other clean meat ventures have relied on fetal bovine serum, derived from the blood of animals, to help grow and duplicate animal cells for their products. FBS is highly expensive, however, and its use rankles animal rights and climate activists.

Because Animals developed its own animal-free formulation, and Liao believes the technology will be broadly applicable, possibly beyond pet foods.

Falconer, for the time being, says she is focused on the growing pet food category.

The CEO decided to pursue sustainable pet food while she was working as a postdoctoral research fellow at Stanford University's School of Medicine, she recalls.

Microbiologist Shannon Falconer started Because Animals. to bring cellular agriculture to the pet food industry.

Courtesy: Because, Animals.

Research animals were all around her, and she didn't have the expertise to eliminate scientists' need of them. But with her advanced degrees in microbiology and biochemistry, she knew how to cultivate different types of microorganisms and cells in a lab.

Falconer saw the potential to use her scientific skills to reduce or remove animals from the food supply chain. But she also felt that in her own diet, there were many options to choose from both at restaurants and grocery stores. She's mostly a lentils and tofu person, she says, but is a big fan of Impossible Foods' plant-based substitutes for meat products.

"We can always use more," the CEO said, "and I am happy when there are even more alternatives. But there was absolutely nothing for my cats and virtually nothing for dogs."

Falconer initially wondered if pet food was a big enough market to tackle, and how much of an environmental difference it could make to shift meat production for pet food toward cultured ingredients.

Livestock agriculture was responsible for the equivalent of260.54 million metric tons of carbon dioxide emissions in the U.S. in 2019, according to the most recent available EPA data.

The amount of pet food consumed pales in comparison with human meat consumption, Falconer discovered. But pet food is produced from leftovers in the global meat supply chain, including tons of meat that couldn't be sold for human consumption, and meat from fallen animals that die in transit, or from suffocation in farming facilities or from disease.

"All that meat gets shunted into pet food," Falconer said, "And it allows animal agriculture to stay afloat without making any big changes.

Today, the pet food market is growing, buoyed by increased adoption of dogs and cats by millennials, and greater awareness of health benefits through nutrition for pets. According to Grand View Research, the pet food market should grow to around $90.4 billion by 2025.

If Because Animals has the impact Falconer is looking for, a significant portion of that will shift to clean meat and other sustainable products soon. The company's next challenge will be scaling up to a larger commercial kitchen, while continuing to develop new, clean meat pet foods.

Correction: Livestock agriculture was responsible for the equivalent of 260.54 million metric tons of carbon dioxide emissions in the U.S. in 2019.

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Meet the company making mouse meat cat treats without harming animals - CNBC

August 13, 2021

LUMBERTON Area health care providers are urging pregnant and nursing women to receive a COVID-19 vaccination.

Only about 22% of pregnant women have received at least one dose of a COVID-19 vaccine, according to the federal Centers for Disease Control and Prevention. One reason could be conflicting information that causes uncertainty about the safety of the vaccine, an issue that has been before the medical community for less than two years.

There are, understandably, no long-term studies to validate safety at this time, said Don McKinley, M.D., doctor of obstetrics and gynecology at UNC Health Southeastern.

In order to break through the fog of fear, UNC Health Southeastern physicians and caregivers discuss the benefits and risks of getting a vaccination with patients. One fact presented to patients is the danger COVID-19 presents to pregnant women.

According to the CDC, Pregnant and recently pregnant people are more likely to get severely ill with COVID-19 compared with non-pregnant people. If you are pregnant, you can receive a COVID-19 vaccine. Getting a COVID-19 vaccine during pregnancy can protect you from severe illness from COVID-19. If you have questions about getting vaccinated, a conversation with your healthcare provider might help, but is not required for vaccination.

There is no current evidence that any vaccines, including COVID-19 vaccines, cause fertility problems, according to the CDC. But, data are limited.

Claims linking COVID-19 vaccines to infertility are unfounded and have no scientific evidence supporting them, information given to UNC Health Southeastern patients reads in part.

UNC Health Southeastern staffers tell patients that the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM), the two leading organizations representing specialists in obstetric care, recommend that all pregnant individuals be vaccinated against COVID-19. The organizations support of vaccination during pregnancy reflects evidence demonstrating the safe use of the COVID-19 vaccines during pregnancy from tens of thousands of reporting individuals over the past several months, and the current low vaccination rates and concerning increase in cases.

Data have shown that COVID-19 infection puts pregnant people at increased risk of severe complications and even death, a release from the ACOG and the SMFM reads in part.

The two medical organizations point to the increased risk posed by the COVID Delta variant as another reason pregnant women should get vaccinated. People who have recently delivered and were not vaccinated during pregnancy also are strongly encouraged to get vaccinated as soon as possible, according to the two medical organizations.

ACOG encourages its members to enthusiastically recommend vaccination to their patients. This means emphasizing the known safety of the vaccines and the increased risk of severe complications associated with COVID-19 infection, including death, during pregnancy, said Dr. J. Martin Tucker, president of ACOG. It is clear that pregnant people need to feel confident in the decision to choose vaccination, and a strong recommendation from their obstetriciangynecologist could make a meaningful difference for many pregnant people.

UNC Health Southeastern doctors and other caregivers tell their patients there are risks, as there are with all immunizations, according to the health care system. There are mild side effects. They include injection side reactions, fatigue, chills, muscle pain, joint pain, headache and fever.

So far, the data show no increased risk of miscarriage, birth defects, preterm birth, or stillbirth, said Dr. Stuart Shelton, Cape Fear Valley Perinatologys Maternal Fetal Medicine specialist. Basically, theres no increased risk of any adverse pregnancy outcomes. Data are still being collected and analyzed.

Shelton is the only maternal fetal medicine specialist, or perinatologist, in Cumberland County, and has been practicing in Fayetteville for 19 years, according to Cape Fear Valley Health.

I think the vaccine is safe, and I tell the patient that her risk of pregnancy complications is much higher if she gets COVID infection than it is with the vaccine, Shelton said. And right now, we dont know of any increased risks associated with the vaccine. If it was one of my family members or friends, I would highly recommend they get the vaccine without any reservation.

In a bid to collect more data on the issue, the CDC has established the v-safe COVID-19 Vaccine Pregnancy Registry and is inviting people to participate.

The registry is collecting health information from people who received COVID-19 vaccination in the periconception period (within 30 days before last menstrual period) or during pregnancy. The information is critical to helping people and their healthcare providers make informed decisions about COVID-19 vaccination. Participation is voluntary, and participants may opt out at any time, according to the CDC.

People wanting to participate must be enrolled in v-safe, a smartphone-based tool that uses text messaging and web surveys to provide personalized health check-ins after a person receives a COVID-19 vaccine. Through v-safe, a person can quickly tell CDC about any side effects after getting a COVID-19 vaccine.

Depending on your answers to the web surveys, someone from CDC may call to check on you and get more information. V-safe will also remind you to get your second COVID-19 vaccine dose if you need one, the CDC website reads in part.

Anyone who wants to participate in v-safe can register online at https://www.cdc.gov/coronavirus/2019-ncov/vaccines/safety/register-for-v-safe.html

The New England Journal of Medicine included v-safe data collected from Dec. 14, 2020, to Feb. 28 in an article published on April 21.

The results were, A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS (Vaccine Adverse Event Reporting System), the most frequently reported event was spontaneous abortion (46 cases).

The conclusion was that preliminary findings did not show obvious safety signals among pregnant people who received mRNA COVID-19 vaccines.

According to the CDC, mRNA vaccines teach cells how to make a protein that triggers an immune response inside the body. The benefit of mRNA vaccines is people vaccinated gain protection without risking the serious consequences of getting sick with COVID-19.

However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes, the Journal of Medicine article reads in part.

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Petco Love awards $2,000 grant to Blind Cat Rescue & Sanctuary - The Robesonian

Every Wednesday at 8:30we're joined by John Perreault, Executive Director of theBerkshire Humane Societyto discuss all the happenings at their Barker Road facility, plus talk about their Pet of the Week.

Hello there, I'm Sofia! I am the absolute sweetest girl looking for a loving home to call my own. I can be very selective with the dogs that I choose to be friends with, and would not be a fan of living with another dog. However, when I'm out on walks, I do not bark or react to other dogs.

People are my favorite! I have yet to meet a person that I don't love, and I will show my affection with kisses and snuggles! I am fully house-trained and keep my kennel clean overnight too. And if you aren't sold on me yet, I also love to go out on hikes and for long walks with my people! I have never been around children, so a home with teens and up would be ideal. I cannot live with cats. I currently weigh 43 pounds.

If you are interested in meeting me, the lovely Sofia, or would like some more information, please call the kennel staff at (413) 447-7878 ext.126.

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

Below, find out where 25 of the most infamous crimes in history took place and what the locations are used for today. (If they've been left standing.)

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Live 95.9 Pet Of The Week: Meet Sofia - Live 95.9

COVID-19 isnt the Only Virus to be on the Lookout for West Nile is Back

The West Nile Virus has been detected in a batch of mosquitos that were collected in Salem, New Hampshire on August 3 according to wmur.com. Time to get out that insect repellent. The New Hampshire Department of Health and Human Services has elevated the risk for the virus in our area to low. Although the risk may be listed as low it is still something to be aware of. You dont want to get West Nile Virus.

Dr. Benjamin Chan, a state epidemiologist said in a press release, Until there is a statewide mosquito-killing frost, it remains important for everybody to take steps to prevent mosquito bites, including wearing long sleeves, using an effective mosquito repellant on exposed skin, and avoid outdoor activities at dawn and dusk when the mosquitos are most active, according to reporting by wmur.com. Another reason to avoid mosquitos is the risk of Eastern Equine Encephalitis and Jamestown Canyon virus. A New Hampshire resident died just last month after contracting the Jamestown Canyon virus.

If you are bitten by a mosquito carrying the West Nile Virus, you most likely not see symptoms for about a week. The symptoms can feel like the flu, you can have a fever and muscle aches, and fatigue. Some people just get mild symptoms while others can experience a more serious central nervous system disease. Contact your healthcare provider if you have any doubts or are experiencing symptoms. I get so freaked out by sharks when the real threat from viruses is invisible to the naked eye. Just something else to worry about as if I dont have enough. Wear your insect repellent.

Since we are on the topic of getting bit look at this

Here in Maine, there are plenty of critters that can take a bite out of you if they do desire.

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

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Be Very Careful the West Nile Virus Detected in Mosquitos in Salem New Hampshire - wokq.com

I'm pretty sure you got the alert on your phone this morning but if you didn't, August 17th is Black Cat Appreciation Day.

This is not to be confused with the October 27th holiday of National Black Cat Day. What's the difference? No one knows but these little guys all deserve their day in the sun. But not too much sun. According to this Mental Floss article, when a black cat spends too much time in the sun, it can dye the pigments causing natural striping or spotting to occur. It's pretty complicated and you should check out the article for a completeexplanation.

One other fact I learned from the article is that black cats aren't bad luck in every culture. Sometimes they're good luck.

If you're a single woman in Japan, owning a black cat is said to increase you number of suitors: if you're in Germany and one crosses your path from left to right, good things are on the horizon.

Seriously, there are 8 black cat facts on that list and at lest 7 are interesting.

I went to the Winnebago County Animal Services site and found that they had quite a few black cats up for adoption. I counted at least 10 without getting too loose with the definition of a "black" cat.

Here's a list of 10 feline friends you can bring into your house to hopefully change your luck for the better.

Darling is a 3-year-old spayed Domestic Shorthair. She also has amazing eyes.

Sami is a 2-year-old neutered Domestic Shorthair. He has tufts of white to contrast the deep black. Very cool looking cat.

Zach is a 1-year-old Domestic Longhair. This isn't the most flattering angle of Zach I'm sure. Perhaps for the cat owner that likes their distance.

The website says this is a 1-year-old male Domestic Shorthair, but I'm pretty sure that's a pug. Either way it looks like Whiskers needs some care so he can relax.

Salem

Salem is a 2-Year-Old spayed Domestic Shorthair and if I'm being honest looks magnificent. I don't even really like cats and I'd like this cat. Her "resting queen-face" is amazing. 10/10 as far as cats go.

Raspberry is a 4-month-old female Domestic Medium Hair. Raspberry appears to be a kitten. Very cute.

Monty is a 2-year-old neutered Domestic Shorthair. Did I bend the rules a little by letting this white nosed cat into the mix? Maybe. But I loved this guy's look. He's only 2 years old and he'll be having none of your s^%t today. I respect that.

Lana is a 2-year-old spayed Domestic Shorthair. I have no idea what the frame of reference we're looking at Lana in, but she appears to be quite small. Perhaps a runt? Runts are great pets.

Keke is a 3-year-old spayed Domestic Shorthair. Is Keke totally black? No but that's another face I felt the need to share.

You can apply onlineand they'll get back to you soon. Rescues are literally the best. Max came from a shelter and is everyone's favorite no matter where I take him.

I know you didn't ask but yes, he IS a very good boy.

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

A trip to the zoo to see the animals is always a highlight to my family's summer. This year, Belvidere's Summerfield Zoo has many baby animals you need to see.

Follow this link:
Here Are 10 Adoptable Black Cats In Rockford. Happy Black Cat Appreciation Day! - 1440wrok.com

10 of 14 Patients in FT596 Single-Dose Escalation Cohorts 2 and 3 Achieved Objective Response; 7 Patients Achieved Complete Response, including 2 of 3 Patients Treated with FT596 in Combination with Rituximab Following Autologous CD19 CAR T-cell Therapy

8 of 11 Patients in FT516 Multi-Dose Escalation Cohorts 2 and 3 Achieved Objective Response, including 6 Patients that Achieved Complete Response; 5 of 8 Responders Continue in Ongoing Response at Median Time of 5.2 Months

FT596 and FT516 Treatment Regimens were Well-tolerated; No Dose-limiting Toxicities, and No Adverse Events of Any Grade of ICANS or GVHD, were Observed; Two Low-grade Adverse Events of CRS were Reported in FT596 Single-Dose Escalation Cohorts 1 and 2

Management to Host Virtual Event Today at 4:30 PM Eastern Time

SAN DIEGO, Aug. 19, 2021 (GLOBE NEWSWIRE) -- Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer, today highlighted positive interim clinical data from the Companys FT516 and FT596 programs for patients with relapsed / refractory B-cell lymphoma. FT516 is the Companys universal, off-the-shelf natural killer (NK) cell product candidate derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor, which is designed to maximize antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. The Companys FT596 program incorporates both the hnCD16 Fc receptor and a chimeric antigen receptor (CAR) targeting CD19, which is designed to enable multi-antigen targeting of tumor cells, as well as an IL-15 receptor fusion (IL-15RF) to enhance NK cell activity and survival.

We are very pleased with the interim safety, response rates, and durability of responses observed in our ongoing clinical studies of FT516 and FT596 for the treatment of patients with relapsed / refractory B-cell lymphomas. These data continue to demonstrate that our off-the-shelf, iPSC-derived NK cell product candidates can uniquely deliver substantial therapeutic benefit and expand patient access to cell-based cancer immunotherapies, said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. At this time, we are initiating multiple indication-specific, dose-expansion cohorts to broadly assess FT516 in combination with CD20-targeted monoclonal antibody regimens, including in patients that have experienced disease progression following autologous CD19-targeted CAR T-cell therapy. In addition, early clinical data with the single-dose FT596 treatment schedule have shown robust 30-day response rates and we look forward to further assessing both single-dose and multi-dose treatment regimens to validate its potential best-in-class therapeutic profile.

FT596 ProgramThe ongoing clinical trial in relapsed / refractory B-cell lymphoma is assessing a single dose of FT596 as monotherapy (Monotherapy Arm) and in combination with a single dose of rituximab (375 mg/m2) (Combination Arm) following three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine). As of the data cutoff date of June 25, 2021, 10 patients in the Monotherapy Arm and 10 patients in the Combination Arm were evaluable for assessment of safety and efficacy in the first, second, and third dose cohorts of 30 million cells (n=3 each), 90 million cells (n=4 each), and 300 million cells (n=3 each), respectively (see Table 1). Patients had received a median of four prior lines of therapy and a median of 2.5 prior lines containing CD20-targeted therapy. Of the 20 patients, 12 patients (60%) had aggressive B-cell lymphoma, 10 patients (50%) were refractory to most recent prior therapy, and seven patients (35%) were previously treated with autologous CD19-targeted CAR T-cell therapy.

In the second and third single-dose cohorts of the Monotherapy and Combination Arms comprising a total of 14 patients, 10 of 14 patients (71%) achieved an objective response, including seven patients (50%) that achieved a complete response (CR), as assessed by PET-CT scan per Lugano 2014 criteria on Day 29 following FT596 dosing. Eight of 10 patients (80%) that had not previously received CD19-targeted CAR T-cell therapy achieved an objective response, including five patients (50%) that achieved CR. Two of four patients (50%) that had previously received CD19-targeted CAR T-cell therapy, both of whom were treated in the Combination Arm, achieved a CR. In the first single-dose cohorts of the Monotherapy and Combination Arms comprising a total of six patients, only one patient achieved an objective response, suggesting dose-response treatment effects for FT596. The ongoing dose-escalation study of FT596 is currently enrolling patients in the fourth single-dose cohort of 900 million cells in each arm.

The FT596 treatment regimens were well tolerated. No dose-limiting toxicities, and no treatment-emergent adverse events (TEAEs) of any grade of immune effector cell-associated neurotoxicity syndrome (ICANS) or graft-versus-host disease (GVHD) were observed. Two low-grade adverse events (one Grade 1, one Grade 2) of cytokine release syndrome (CRS) were reported, both of which occurred concurrently with other confounding clinical events and resolved on the same day of onset.

FT596 Patient Case StudiesThe multi-antigen targeting functionality of FT596 is designed to uniquely address tumor heterogeneity and overcome antigen escape, and has the potential to drive responses in patients that might not effectively be treated with single-antigen targeted modalities, such as monoclonal antibodies, bispecific engagers and CAR T-cell therapies. The following are two case studies from the clinical trial:

Re-treatment with Second FT596 CycleThe FT596 protocol currently allows for the re-treatment of eligible patients with a second, single-dose cycle subject to consent of the U.S. Food and Drug Administration (FDA). All requests by the Company for re-treatment were approved by the FDA. Of note, based on review of data submitted to date to the FDA, the Company is amending its FT596 clinical protocol at the FDAs recommendation to allow for re-treatment with a second FT596 cycle without requiring the agencys consent.

In second and third single-dose cohorts of the Monotherapy and Combination Arms as of the data cutoff date, four patients with CR at the end of the first single-dose cycle were re-treated, all of whom remained in CR following disease assessment at the end of the second cycle, and an additional four patients were re-treated and had not yet been assessed for response. The second, single-dose FT596 cycle was well tolerated, and no events of any grade of CRS, ICANS, or GVHD were observed.

FT516 ProgramThe clinical trial in relapsed / refractory B-cell lymphoma is assessing FT516 in an off-the-shelf treatment regimen of up to two cycles, with each cycle consisting of three days of conditioning chemotherapy (500 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine), a single dose of rituximab (375 mg/m2), and three weekly doses of FT516 each with IL-2 cytokine support. The FT516 treatment regimen is designed to be administered in the outpatient setting. Dose escalation is currently ongoing in the fourth multi-dose cohort of 900 million cells per dose.

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting held in June, the Company highlighted positive interim clinical data for 11 patients treated in the second and third multi-dose cohorts of 90 million cells per dose (n=4) and 300 million cells per dose (n=7). Patients had received a median of three prior lines of therapy and a median of two prior lines containing CD20-targeted therapy. Of the eleven patients, eight patients had aggressive B-cell lymphoma, five patients were refractory to their most recent prior therapy, and four patients were previously treated with autologous CD19 CAR-T cell therapy. No dose-limiting toxicities, and no FT516-related serious adverse events or FT516-related Grade 3 or greater adverse events, were observed. The FT516 treatment regimen was well tolerated, and no TEAEs of any grade of CRS, ICANS, or GVHD were reported.

Ongoing Response AssessmentOf the 11 patients treated in the second and third multi-dose cohorts, eight patients (73%) achieved an objective response, including six patients (55%) who achieved CR, as assessed by PET-CT scan per Lugano 2014 criteria on Day 29 following the second FT516 treatment cycle. Notably, two of four patients (50%) previously treated with autologous CD19 CAR-T cell therapy achieved CR. At three months following first infusion, all eight responders maintained their response without further therapeutic intervention (3-Month Rate of 73% OR and 55% CR). As of the data cutoff date of July 7, 2021:

FT516 Patient Case StudyThe ASCO presentation featured a case study of a 36-year old male with triple-hit, high-grade B-cell lymphoma with rearrangements of MYC, BCL2, and BCL6 genes. The patient was refractory to all prior lines of therapy with the exception of autologous CD19 CAR T-cell therapy, for which a complete response of two months duration was achieved. The patient was most recently refractory to an investigational CD20-targeted T-cell engager and presented with bulky lymphadenopathy with the largest lesion measuring approximately 10 centimeters. The first FT516 treatment cycle resulted in a complete response with resolution of all metabolically active disease and 85% reduction in the size of target lesions. The patient received a second FT516 treatment cycle, after which the response assessment continued to show complete response. As of the data cutoff date of July 7, 2021, the patients most recent assessment at 4.9 months showed MRD negativity, confirming a profound CR.

Today's WebcastThe Company will host a live audio webcast today, Thursday, August 19, 2021 at 4:30 p.m. ET to review interim clinical data for the Companys FT516 and FT596 off-the-shelf, iPSC-derived NK cell programs. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company's website at http://www.fatetherapeutics.com. The archived webcast will be available on the Company's website beginning approximately two hours after the event.

About Fate Therapeutics iPSC Product PlatformThe Companys proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Companys first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Companys platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics iPSC product platform is supported by an intellectual property portfolio of over 350 issued patents and 150 pending patent applications.

About FT516FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in a multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in a multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About FT596FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors enhances cytotoxic activity, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab, and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

About Fate Therapeutics, Inc.Fate Therapeutics is a clinical-stage biopharmaceutical company dedicated to the development of first-in-class cellular immunotherapies for patients with cancer. The Company has established a leadership position in the clinical development and manufacture of universal, off-the-shelf cell products using its proprietary induced pluripotent stem cell (iPSC) product platform. The Companys immuno-oncology pipeline includes off-the-shelf, iPSC-derived natural killer (NK) cell and T-cell product candidates, which are designed to synergize with well-established cancer therapies, including immune checkpoint inhibitors and monoclonal antibodies, and to target tumor-associated antigens using chimeric antigen receptors (CARs). Fate Therapeutics is headquartered in San Diego, CA. For more information, please visit http://www.fatetherapeutics.com.

Forward-Looking StatementsThis release contains "forward-looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995 including statements regarding the safety and therapeutic potential of the Companys iPSC-derived NK cell product candidates, including FT516 and FT596, the Companys plans and timelines for its ongoing and planned clinical studies, and the expected clinical development plans for FT516 and FT596. These and any other forward-looking statements in this release are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, the risk that results observed in studies of its product candidates, including interim results and results from earlier studies, may not be predictive of final results or results observed in ongoing or future studies involving these product candidates, the risk of a delay in the initiation of, or in the enrollment or evaluation of subjects in, any clinical studies, the risk that the Company may cease or delay clinical development of any of its product candidates for a variety of reasons (including requirements that may be imposed by regulatory authorities on the initiation or conduct of clinical trials, the amount and type of data to be generated, or otherwise to support regulatory approval, difficulties or delays in subject enrollment and continuation in current and planned clinical trials, difficulties in manufacturing or supplying the Companys product candidates for clinical testing, and any adverse events or other negative results that may be observed during preclinical or clinical development), and the risk that its product candidates may not produce therapeutic benefits or may cause other unanticipated adverse effects. For a discussion of other risks and uncertainties, and other important factors, any of which could cause the Companys actual results to differ from those contained in the forward-looking statements, see the risks and uncertainties detailed in the Companys periodic filings with the Securities and Exchange Commission, including but not limited to the Companys most recently filed periodic report, and from time to time in the Companys press releases and other investor communications.Fate Therapeutics is providing the information in this release as of this date and does not undertake any obligation to update any forward-looking statements contained in this release as a result of new information, future events or otherwise.

Contact:Christina TartagliaStern Investor Relations, Inc.212.362.1200christina@sternir.com

More:
Fate Therapeutics Announces Positive Interim Clinical Data from its FT596 and FT516 Off-the-shelf, iPSC - GlobeNewswire

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Oncternal Therapeutics, Inc.(NASDAQ:ONCT)Q22021 Earnings CallAug 05, 2021, 5:00 p.m. ET

Operator

Greetings, and welcome to the Oncternal Therapeutics, Incorporated's second-quarter 2021 financial results call. [Operator instructions] As a reminder, this conference is being recorded. It is now my pleasure to introduce Richard Vincent, chief financial officer. Thank you.

You may begin.

Rich Vincent -- Chief Financial Officer

Thank you, Darryl. Good afternoon, everyone, and thank you for joining us today. Joining me on this call this afternoon are our president and CEO, Dr. James Breitmeyer; and our CMO, Dr.

Salim Yazji. We welcome all of you. Today's call includes a business update, a discussion of our 2021 second-quarter financial results, as well as our upcoming milestones, which will be followed by Q&A. Today's press release and a replay of today's earnings call will be available on the investor relations section of Oncternal's website for at least the next 30 days.

We also filed our 10-Q for the second quarter of 2021 earlier today. Please note that certain information discussed on today's call is covered under the safe harbor provisions of the Private Securities Litigation Reform Act. We will be making forward-looking statements during this call about future events, such as our business and product development strategies and future financial and operating performance. Our actual results could differ materially from those stated or implied by these forward-looking statements due to risks and uncertainties associated with our business.

These forward-looking statements should be considered in conjunction with and are qualified by the cautionary statements contained in today's press release and our SEC filings, including our Form 10-Q for the quarter ended June 30, 2021. This conference call contains time-sensitive information that is accurate only as of the date of the live broadcast, August 5, 2021. We undertake no obligation to revise or update any forward-looking statements to reflect events or circumstances occurring after the date of this conference call. With that, it's my pleasure to hand the call over to our CEO, Dr.

Jim Breitmeyer.

Jim Breitmeyer -- Chief Executive Officer

Thank you, Rich, and good afternoon, everyone. At Oncternal, we are committed to developing novel treatments for patients with cancer who have critical unmet medical needs. We're advancing a robust product pipeline with clinical and preclinical product candidates that target several such cancer indications. We are particularly pleased with the progress made during the second quarter of 2021 to advance the development of cirmtuzumab, our investigational, potentially first-in-class humanized monoclonal antibody that binds with high affinity to a biologically important epitope on ROR1, also known as receptor tyrosine kinase-like orphan receptor one.

Encouraging updated interim clinical trial results with cirmtuzumab plus ibrutinib in patients with mantle cell lymphoma, or MCL, and chronic lymphocytic leukemia, or CLL, were presented in a poster session at the ASCO 2021 annual meeting. In addition, in July 2021, we opened a new treatment cohort of our ongoing Phase 1/2 study to evaluate cirmtuzumab plus ibrutinib in patients with MCL who are refractory to prior BTK inhibitor treatment, including ibrutinib, acalabrutinib or zanubrutinib; and to include patients who are at high risk for progression, having had an inadequate response to ibrutinib that is only achieving stable disease or a partial response. Our CMO Salim will provide additional details on each of these. We also have an ongoing dialogue with the U.S.

FDA concerning the potential registration pathway for cirmtuzumab, and we expect further feedback on a potential pivotal study design this year. ROR1 has been an -- become an increasingly visible target in the oncology space and has been the subject of M&A activity, including the acquisition of VelosBio by Merck & Co. VLS-101, VelosBio's ROR1-targeted antibody drug conjugate, or ADC, was originally invented and developed add-on terminal, and it incorporates the cirmtuzumab antibody to target ROR1. We believe we have one of the most advanced and diverse pipelines targeting ROR1 in the industry today.

We also continue to collaborate on two investigator-sponsored clinical studies of cirmtuzumab at UC San Diego. First, a Phase 1b clinical trial of cirmtuzumab in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced unresectable breast cancer; and second, a Phase 2 clinical trial of cirmtuzumab in combination with venetoclax, a BCL2 inhibitor in patients with relapsed/refractory CLL. UCSD finished enrollment for the breast cancer study in the second quarter of this year. So moving on to our immuno-oncology cell therapy programs, we continue to make progress on our novel ROR1-targeting CAR-T and CAR-NK cell therapy candidates, moving them from the laboratory toward the clinic as planned.

We are very encouraged by the advancement of our cell therapy efforts, including successful recruitment of the internal team and external scientific advisors; preclinical activities with the Karolinska Institute in Stockholm, Sweden; development and manufacturing activities with Lentigen Technology and Miltenyi Biotech; our research collaboration with UC San Diego; and our development partnership with Shanghai Pharma Limited in Greater China. We are tremendously excited by the potential of our cell therapy program targeting ROR1, which may allow for the selective targeting of tumor cells that express ROR1 while sparing healthy tissues. We also advanced the development of TK216, our investigational targeted small molecule inhibitor of the E26 transformation specific, or ETS, family of oncoproteins. We presented encouraging interim clinical data for TK216 in patients with relapsed or refractory Ewing sarcoma in an oral session at the ASCO 2021 meeting.

Based on the data, we added an expansion cohort with an optimized dosing schedule. Salim will provide additional details on this program as well. During this past quarter, we further strengthened our executive team with two key additions in the medical and business fronts. Dr.

Salim Yazji, joining us on the call now, is our new chief medical officer. Salim brings over 25 years of experience in both industry and academic settings, leading global oncology development and regulatory strategy throughout all phases of development, including various product approvals. Pablo Urbanejaas joined us as our SVP of corporate development. Pablo is a seasoned biotech professional with a solid track record in corporate strategy and licensing, and he will lead our expanding strategy portfolio and business development functions at Oncternal.

With this, I will now turn the call over to Salim to provide more color on our clinical programs.

Salim Yazji -- Chief Medical Officer

Thank you, Jim. Good afternoon, everyone. At this year's ASCO meeting, we announced updated clinical data for cirmtuzumab in combination with ibrutinib. In patients with relapsed/refractory MCL enrolled in our ongoing Phase 1/2 trial, the data cutoff at that time was April 16.

The best objective response, complete or partial response rate, or ORR, was 83% for these heavily pretreated patients with MCL treated with cirmtuzumab plus ibrutinib, which compares favorably to historical ORR of 66% for ibrutinib monotherapy. Seven of the 18 evaluable patients, or 39%, had achieved a complete response, or CR, by chip and criteria, one of which was a complete metabolic response, CMR, by pet scan. These CRs remained durable for eight to 30-plus months. This compares favorably to the historical CR rate of 20% for ibrutinib monotherapy.

The media progression-free survival, PFS, and overall survival, OS, were not reached for MCL patients. And the PFS estimate at two years was approximately 60% with a median follow-up of 18.9 months. This compares favorably to the historical PFS of ibrutinib monotherapy of approximately 30% with a median follow-up of 24 months. For patients with CLL, the ORR was 94%, and five patients had achieved the clinical criteria for complete responses with a bone marrow confirmation pending in one patient.

The median PFS and OS has not been reached for CLL patients. And the PFS estimate at two years was approximately 82% with the median follow-up of 22.1 months. The combination of cirmtuzumab and ibrutinib continues to be well-tolerated with the safety profile consistent with or slightly improved compared to the historical data for ibrutinib monotherapy. For example, in patients with MCL Grade 3 and 4 neutrofil decrease was documented in 11.5% of the patients with cirmtuzumab plus ibrutinib, compared to 29% for ibrutinib alone from its registrational study.

We and our study investigators continue to be particularly impressed by the response in heavily pretreated patients. Six patients with MCL who has relapsed following prior autologous stem cell transplant, or CAR-T, therapy, were enrolled in our study, and all six of them responded to the combination of cirmtuzumab and ibrutinib. Four patients achieved complete response, and two patients achieved partial response. All four patients who had received prior treatment with ibrutinib responded to the treatment with cirmtuzumab and ibrutinib with the two CRs and two PRs.

We continue to support our Phase 1b investigator-initiated clinical trial in combination with paclitaxel for the treatment of women with HER2-negative metastatic or locally advanced undetectable breast cancer. At AACR in April 2021, the UC San Diego investigators presented results showing an objective response rate of 57% with an encouraging toxicity profile. These results were consistent with the previously reported interim results of the study and compared favorably to the historical results of single-agent paclitaxel, particularly for patients such as these who had received a median over six prior therapy for metastatic disease. As Jim mentioned, this trial was fully enrolled for a total of 15 evaluable patients.

The results are expected to be presented at the scientific conference or publication. Also, at AACR, we presented data from preclinical study, investigating cirmtuzumab in combination with chemotherapeutic agents, cisplatin and paclitaxel, used to treat high-grade serious ovarian cancer, HGSOC, an endometrial cell line in vitro. Cirmtuzumab demonstrated single-agent activity and enhanced the anti-corrosive effect of chemotherapeutic agents in both ovarian and endometrial cancer cell models, including platinum-resistant ovarian cancer. Our program to develop TK216, our ETS family inhibitor, continues to progress.

At this year's ASCO meeting, we presented an updated clinical data from our ongoing Phase 1/2 trial of TK216 for patients whose relapsed/refractory Ewing sarcoma, and the data cut for that was April 22. The data remains consistent and confirm and extend previous results. Two patients who achieved CR remain with no evidence of disease, one for over 24 months and the other for over 14 months on a study. The treatments continue to be well-tolerated with reversible myelosuppression as the most common side effect.

Based on our encouraging data and KOLs' feedback, in July 2021, we added a new Phase 2 expansion cohort, targeting Ewing sarcoma patients to evaluate clinical response to a single-agent TK216 using an optimized dosing regimen, treating for 28 days per cycle to intensify the amount of TK216 administered over time. I will now turn the call over to Rich Vincent to review financial results and upcoming milestones.

Rich Vincent -- Chief Financial Officer

Thank you, Salim. In October 2017, CIRM awarded an $18.3 million grant to researchers at the UC San Diego School of Medicine to advance our Phase 1/2 clinical trial, evaluating cirmtuzumab in combination with ibrutinib for the treatment of patients with B-cell lymphoid malignancies, including MCL and CLL. We are conducting this study in collaboration with UC San Diego and expect to receive approximately $14 million in development milestones under research sub awards throughout the award period. In conjunction with this award, our grant revenue was $0.9 million for the second quarter ended June 30, 2021.

Our total operating expenses for the quarter ended June 30, 2021, were $8.6 million, including $1.8 million in noncash stock-based compensation. Research and development expenses for the quarter totaled $5.2 million. And general and administrative expenses totaled $3.4 million. Net loss for the second quarter was $7.7 million or a loss of $0.16 per share basic and diluted.

As of June 30, we had $103.7 million in cash and cash equivalents. We believe these funds will be sufficient to support our operations into 2023. As of June 30, we had 49.4 million shares of common stock outstanding. With respect to upcoming milestones for our cirmtuzumab program, we expect an interim clinical data update for the ongoing Phase 1/2 study in MCL and CLL at a scientific conference in the fourth quarter of 2021, a clinical data update from the fully enrolled ongoing breast cancer Phase 1b IST study, an FDA interaction update regarding a potential registration trial of cirmtuzumab in patients with MCL and further preclinical data in additional ROR1-expressing tumors.

On the cell therapies front, we are advancing our ROR1 CAR-T program to treat the first patient in the first half of 2022. For our TK216 program, we expect an interim clinical data update for the ongoing Phase 1/2 expansion cohort in Ewing sarcoma at a scientific conference in the fourth quarter of 2021, as well as additional preclinical data and other ETS-driven tumors. Now I will turn the call back over to Jim.

Jim Breitmeyer -- Chief Executive Officer

Thank you, Rich. In closing, this past quarter, we presented very encouraging data from our clinical programs. We've strengthened our management team, and we continue to have a strong balance sheet and look forward to multiple potential catalysts in the coming months. Thank you for listening to our presentation today.

With that, I'll turn things back to Darryl for the Q&A portion of this afternoon's call.

Operator

Thank you. [Operator instructions] Our first questions come from the line of Hartaj Singh with Oppenheimer. Please proceed with your questions.

Hartaj Singh -- Oppenheimer & Co. Inc. -- Analyst

Great. Thank you, and thanks for the presentations, gentlemen. Jim, a couple of questions. One is, you sort of talked about earlier or about the potential registrational trial for cirmtuzumab and ibrutinib in MCL.

Could you talk a little bit more about what the comp tours of that could look like, whether it would be in a proper Phase 3 drug trial, Phase 2 number of patients? How large could it be? I know you might not have the full information now, but if you can just sort of give us an idea. And then, in your CAR -- your ROR1 CAR-T program, can you talk a little bit about how do you expect to undertake the manufacturing of that for your patients as you dose them? Will it be sort of localized manufacturing at the various facilities where you're giving the CAR-T? Will it be more centralized manufacturing? And then, I got a quick follow-up. Thank you.

Jim Breitmeyer -- Chief Executive Officer

Thank you for your questions, Hartaj. So your first question regards a potential pivotal trial that we are actively discussing with the FDA. And as I said, we are hopeful that we may reach agreement on a study design during this calendar year. So certain elements are still being discussed.

But with both based on FDA feedback and discussions with KOLs and considering commercial considerations, we do believe that a randomized trial of cirmtuzumab plus ibrutinib versus ibrutinib is by far the most robust and best way to go forward toward approval. We have -- we are also carefully examining the ibrutinib response into -- for patients with MCL. And we believe that there is unmet medical need there where we could have a population of MCL patients that is more likely to progress on ibrutinib, without, we think, having a dramatic reduction in the patient population for eventual commercial rollout. And then, I'd say that we're still -- the statistics are still being discussed with FDA.

But for -- as you can imagine, for a randomized trial, it would probably be in the range of several hundred patients, let's say, low single-digit hundreds of patients, while we work out the particulars. So as far as CAR-T manufacturing is concerned, we have -- as I mentioned, we're working with Miltenyi, and they are developing a very interesting technology that would permit local and regional processing of the cells. And we are looking at, for example, the Miltenyi prodigy system, which is a closed bench-top system where many of the steps to process the T-cells from the patient can be done in a fairly common GMP facility, not requiring brick-and-mortar. So that is -- that's a leading example of what we're considering on the manufacturing side, so that we can do the processing near where the patient will be located.

Hartaj Singh -- Oppenheimer & Co. Inc. -- Analyst

Great, great. Thank you, Jim. And then just a quick question on the preclinical data that you're going to present in the fourth quarter of additional ROR1-expressing tumors. Is that in the solid tumor domain, liquid tumor domain? Or does -- and will you be looking combo or monotherapy there? And thank you for the questions.

Jim Breitmeyer -- Chief Executive Officer

Certainly, Hartaj. So what we -- with our -- with Pablo Urbanejaas joining of the company and his strength in strategic planning, we are doing an extensive review of a number of indications where literature or existing preclinical data suggest that ROR1 inhibition could be clinically meaningful. And it is including both solid and liquid tumors, and it's including both monotherapy and combination therapies. And so with that, we're going to put each of those indications through the ringer pressure test and determine what makes the most sense to proceed with for our upcoming clinical indication or indications.

Hartaj Singh -- Oppenheimer & Co. Inc. -- Analyst

Great, great. Thank you, Jim. I'll get back in the queue.

Jim Breitmeyer -- Chief Executive Officer

Thank you, Hartaj.

Operator

Thank you. Our next questions come from the line of Robert Burns with H.C. Wainwright. Please proceed with your questions.

Robert Burns -- H.C. Wainwright & Co. -- Analyst

Hey, guys, thanks for taking my questions, and congrats on the quarter. Just two for me, if I may. First, you have framed expectations with regard to the update we're expected to see in 4Q for cirmtuzumab plus ibrutinib in MCL. In particular, what the duration of follow-up will look like there? And any incremental data we may see? And then, my second question is, considering the data we've seen within the Phase 1 breast cancer study and now that it's fully enrolled, can you discuss your current thoughts around next steps within breast cancer? Or if you're planning on pivoting to a different indication within the solid tumor space? Thank you.

Jim Breitmeyer -- Chief Executive Officer

Thanks for the question, Rob. I'll answer the second one first and then turn over to Salim for the first one. So breast cancer is going to be one of -- probably at this point, first among several indications that we're looking at in this strategic planning process. And so we are -- we really like the breast cancer results, and they're very encouraging, apparently, double the objective responses compared to paclitaxel alone with a good safety profile.

So that is -- that's certainly something that we'll think hard about building on. So let me turn it over to Salim as far as how much follow-up and what we may be presenting in our next interim update.

Salim Yazji -- Chief Medical Officer

Yes. Thank you, Jim. Actually, I mean, what's gonna happen is we most likely gonna present the data at the next scientific conference. And as you know, we only can present the evaluable patients.

They have to have at least one evaluation after two months of treatment. So we would expect probably a handful of patients, additional patients to be presented at the end of the quarter. As you know now, we only have 18 evaluable patients for MCL and 34 evaluable patients for CLL. So for CLL, we're not gonna have any more patients, but we will have 18 evaluable operations, more than 18 evaluable patients by the end of the quarter.

Robert Burns -- H.C. Wainwright & Co. -- Analyst

Awesome. Thanks for the color there, guys.

Jim Breitmeyer -- Chief Executive Officer

Sure. Thank you, Rob.

Operator

Thank you. Our next questions come from the line of Carl Byrnes with Northland Securities. Please proceed with your questions.

Carl Byrnes -- Northland Securities -- Analyst

Great, thank you, and congratulations on all the progress. Obviously, a number of conferences toward the end of the year, ASH in December, the San Antonio Breast Cancer Symposium also, I believe, in early December and then the CTOS symposium in November. Would you anticipate any presentations prior to those events? And if so, what events might they be? Thanks.

Jim Breitmeyer -- Chief Executive Officer

Thank you, Carl. And you did name the most likely venues for us to present in the fourth quarter. We've presented before their high profile, their great conferences. At this point, we don't have anything before that on the books.

But we always keep our eyes open for opportunities to try to give updates when we can.

Carl Byrnes -- Northland Securities -- Analyst

Great, thanks. That's helpful. And also, looking back to cirmtuzumab for MCL with respect to registrational trial, just kind of assuming for the moment that the PFS number that we find is very high, what might be done in terms of a trial design that wouldn't penalize you, if you will, for having a long PFS? In other words, if we want to accelerate something to market and you've got obviously PFS, progression free survival of two times, what could be done there? Thanks.

Jim Breitmeyer -- Chief Executive Officer

Yes. So great question, Carl. And so what we think is particularly interesting is that we've got a strong objective response rate, and that is an endpoint that has been accepted by the FDA previously for accelerated approval. And then, we have this substantial improvement in progression-free survival, which is an endpoint that has been accepted for full approvals.

And so we're considering that certain patients with MCL on ibrutinib have a shorter progression-free survival than average. And so we may be able to further accentuate the difference in PFS by enrolling a population of MCL patients with unmet medical need.

Carl Byrnes -- Northland Securities -- Analyst

And then, would you also potentially be able to follow that up with kind of a post surveillance for other patient populations to achieve kind of a more reflective PFS?

Jim Breitmeyer -- Chief Executive Officer

Yes. The short answer is yes.

Carl Byrnes -- Northland Securities -- Analyst

Cool. Great. Thanks so much. That's helpful.

Jim Breitmeyer -- Chief Executive Officer

Thank you, Carl.

Operator

Thank you. [Operator instructions] Our next questions come from the line of Kumar Raja with Brookline Capital Markets. Please proceed with your questions.

Kumar Raja -- Brookline Capital Markets -- Analyst

Thanks for taking my questions. With regard to the breast cancer trial, what do we know about the ROR1 expression in the patients who had a partial response? And also, how does the treatment impact their ROR1 expression?

Jim Breitmeyer -- Chief Executive Officer

Salim?

Salim Yazji -- Chief Medical Officer

Yeah, so you're talking about the expression of ROR1 and tumor type? Just to clarify the question.

Kumar Raja -- Brookline Capital Markets -- Analyst

Yeah, I understand that in the breast cancer trial, all of them had ROR1 expression based on IHC. My question is like, is there a cutoff point where you're seeing the partial responses and whether this can be optimized in a future trial, so that you are selective for patients whom you think would be responsive?

Salim Yazji -- Chief Medical Officer

Excerpt from:
Oncternal Therapeutics, Inc. (ONCT) Q2 2021 Earnings Call Transcript - Motley Fool

Big Heart Pet, Inc. the makers of Pup-Peroni Dog Treats (Original Beef & Triple Steak Flavors) has withdrawn, the dog treats because of the presence of mold. specifically, Various lot numbers and sizes of Original Beef Flavor and Triple Steak Flavor Pup-Peroni Dog Treats, with best by dates ranging from Sept. 25, 2022 to Dec. 24, 2022.

Sku info sent by Chewy that was affected:

Pup-Peroni Original Beef Flavor Dog Treats, 38-oz bag 79100830527125211

Best by Date/ Production Code: VariousLot: Various Pup-Peroni Triple Steak Flavor Dog Treats, 38-oz bag 79100589913177938

Best by Date/ Production Code: VariousLot: Various Pup-Peroni Original Beef Flavor Dog Treats, 25-oz bag 7910058371399923

Best by Date/ Production Code: VariousLot: Various Pup-Peroni Triple Steak Flavor Dog Treats, 25-oz bag 79100149810142268

Best by Date/ Production Code: VariousLot: Various

Ina release from the company that makes pup-peroni, the J.M Smucker Company

They have initiated a withdrawal of specific lots of Pup-Peroni Triple Steak Flavor andOriginal Beef Flavor Dog Treats due to an incident involving mold. While we continue to evaluate the issue, thedata we currently have does not suggest a food safety risk and we are coordinating this withdrawal out of anabundance of caution.

The Companies records indicate you have received shipments of impacted products.The company asksthat you examine yourinventories and immediately destroy any impacted product that remains.

Earlier this week, several customers shared photos on Pup-Peronis Facebook page that appeared to show mold on dog treats.

To receive your credit, please complete the Product Destruction/Return Summary form enclosed and send it to the contact identified on theform.

If any product matching the below production information is located at individual stores or distribution centers,please destroy the impacted product, fill out the included Verification of Product Destruction/Return form andsend it to your customer service representative.

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

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Read the original post:
A Well Known Dog Treat Your Pups Love Has Been Withdrawn - WUPE

Every Wednesday at 8:30we're joined by John Perreault, Executive Director of theBerkshire Humane Societyto discuss all the happenings at their Barker Road facility, plus talk about their Pet of the Week.

This week's Pet of the Week is Jerry a long-haired two-year-old domestic long-haired cat looking for his forever home. Jerry is a very sweet cat who often gets overlooked by visitors to the Berkshire Humane Society Purradise location but would make a great companion for almost any household.

If you are interested inJerry or any of the other animals looking for their forever home, please call the Berkshire Humane Society kennel at 413-447-7878, extension 126.

Why do they meow? Why do they nap so much? Why do they have whiskers? Cats, and their undeniably adorable babies known as kittens, are mysterious creatures. Their larger relatives, after all, are some of the most mystical and lethal animals on the planet. Many questions related to domestic felines, however, have perfectly logical answers. Heres a look at some of the most common questions related to kittens and cats, and the answers cat lovers are looking for.

To prepare yourself for a potential incident, always keep your vet's phone number handy, along with an after-hours clinic you can call in an emergency. The ASPCA Animal Poison Control Center also has a hotline you can call at (888) 426-4435 for advice.

Even with all of these resources, however, the best cure for food poisoning is preventing it in the first place. To give you an idea of what human foods can be dangerous, Stacker has put together a slideshow of 30 common foods to avoid. Take a look to see if there are any that surprise you.

Read more:
Berkshire Humane Society Pet of the Week: Meet Jerry - Live 95.9