Can Olema Oncology Prevail Where Other SERDs have Recently Failed?

 Sean Bohen, M.D., Ph.D., president and chief executive officer of Olema Oncology, is excited about the progress his company is making on the development of OP-1250, a potential treatment for metastatic breast cancer.

In a conversation with BioSpace, Bohen pointed out that OP-1250 is both a selective ER degrader (SERD), as well as a complete estrogen receptor (ER) antagonist (next generation CERAN). It’s that combined approach to targeting a tumor that Bohen believes will be critical to the clinical development of OP-1250, which is designed to treat estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer. While there are multiple drugs on the market for breast cancer, Bohen said there is still a “large unmet need” in the space.

“Our competition isn’t another company. Our competition is the disease, and the disease is much craftier than we are,” Bohen said. “There’s an unmet need and a big market out there. Breast cancer is the most common cancer in women.”

As an example, he pointed out that pharma giant Sanofi saw a failure with its cornerstone oncology SERD asset amcenestrant, which flunked a Phase III study in patients with this same type of breast cancer. Sanofi wasn’t alone in seeing a SERD failure. In April, Roche also announced that the Phase II acelERA trial assessing its oral SERD, giredestrant, failed to meet the primary endpoint of progression-free survival in people with a certain form of advanced breast cancer.

Bohen said the space to treat this form of breast cancer is wide open and he’s confident that OP-1250, which is both a SERD and an ER antagonist, has the opportunity to establish a strong clinical reputation. Early data suggests the company is on track. Despite an odd 2021 incidence of what the company called “falsified information” that caused some investors to dump company stock, Bohen has expressed confidence in the development of the asset and its promise as a potential breast cancer treatment.

Last year, ahead of Olema's presentation of data, an individual who claimed to have been a participant in the Phase Ia portion of a clinical study posted data online that the company was forced to refute. That particular individual claimed to have not received a high dose of the medication and said they, therefore, did not see any benefits. The post purportedly contained images from a poster presentation online. When Olema posted its own data that was not as robust as some of what the individual claiming to be a patient shared, the company’s stock cratered.

Olema’s data showed strong proof-of-concept for OP-1250, as well as highly attractive pharmacokinetics and favorable safety data. Among those patients who were treated in the early study, Olema said there were three partial responses, two of which have been confirmed, as well as “robust target lesion reduction up to 100%.” All three responses occurred in patients with ESR1 mutations who had previously received CDK4-6 and aromatase inhibitors, and fulvestrant, a selective estrogen receptor degrader. Bohen said the data demonstrates that OP-1250 is an active drug and achieved sufficient exposure levels to block the ER-mediated cancer cell growth and proliferation signal.

Bohen told BioSpace that he considered the investor reaction that caused company stock to drop by nearly 50% to be an “overreaction” to the falsified data. He speculated that the response was part of the current market environment in biotech that creates significant swings in prices.

He explained that in the Phase Ia single-agent study, there were 41 patients, with most having been heavily pretreated. He said the company did not reach a maximum tolerable dose. Also, Olema saw clear evidence of tumor shrinkage at the starting dose of 30mg. However, there were four cases of Grade IV neutropenia (low white blood cell counts). All four patients discontinued the study and all four recovered. Bohen said the trial investigators dove into the data and have been unable to determine what caused the neutropenia. It does not appear that it is related to the drug itself. “The cases were unusual,” he said.

Earlier this year, Olema presented updated data from the ongoing Phase I/II clinical study that provided strong proof of concept supporting OP-1250’s potential as a once-daily oral monotherapy in women with recurrent, locally advanced or metastatic ER+ / HER2- breast cancer. OP-1250 demonstrated highly attractive pharmacokinetics, favorable tolerability and clear efficacy signals in a heavily pretreated patient population, the company reported.

That data was further supported in a Phase Ib study where OP-1250 was assessed as a monotherapy and also partnered with Pfizer’s Ibrance (palbociclib), a CDK4-6 inhibitor. As a monotherapy, OP-1250 showed favorable tolerability with encouraging anti-tumor activity. There was no grade III or IV neutropenia. 

Bohen said the company aims to select the recommended dose for a Phase II study and soon begin to enroll the trial for these advanced breast cancer patients.

“I really think we’re going to advance the treatment for this form of cancer,” Bohen said. “We are progressing the molecule and we are progressing quickly. We know how to get OP-1250 to patients and improve upon existing care.”

https://www.biospace.com/article/can-olema-oncology-prevail-where-other-serds-have-recently-failed-/

Merck, Emergent, Affinivax and Ocugen Level Up in Vaccine Development

 The week began with positive updates in the vaccine development space against various infectious diseases, including pneumococcal disease, SARS-CoV-2 and a chikungunya virus-like illness. BioSpace highlights four of these below.

Emergent's Chikungunya Virus-Like Particle Vaccine

Emergent BioSolutions published two-year data from its Phase II clinical trial on the immunogenicity and safety of the PXVX0317 vaccine when used on chikungunya virus virus-like particle (CHIKV VLP) naive adults in the United States. The study, which involved 415 participants, achieved the primary endpoint of geometric mean titer of anti-CHIKV neutralizing antibody on day 57. 

The vaccine was found to be well-tolerated and induce a durable serum neutralizing antibody response versus the chikungunya virus for up to two years. CHIKV affects people in over 100 countries and spreads through infected mosquito bites. Symptoms include joint and muscle pain, headache, fever, rashes and joint swelling. 

Details are available online in The Lancet Infectious Diseases journal. 

Merck's Pneumococcal Vaccine Hits Primary immunogenicity Targets

Merck announced favorable results from the Phase I/II study of V116-001, its investigational 21-valent pneumococcal conjugate vaccine. The trial is assessing the vaccine's tolerability, safety and immunogenicity in two age groups: 18 to 49 for Phase I and 50-plus for Phase II. 

V116-001 was observed to be well-tolerated and had met primary immunogenicity goals, with researchers comparing its impact to the current market player Pneumovax 23. Responses were observed 30 days after the vaccine was given. 

The vaccine received Breakthrough Therapy designation in early 2022 from the U.S. Food and Drug Administration to prevent invasive pneumococcal disease (IPD) and pneumococcal pneumonia from 21 Streptococcus pneumoniae serotypes in adults ages 18 and up. 

"Consistent with our portfolio strategy, V116 is designed to specifically target serotypes that are responsible for 85 percent of all invasive pneumococcal disease in individuals aged 65 and over in the United States as of 2019," Dr. Eiav Barr, SVP and chief medical officer at Merck Research Laboratories noted. 

Affinivax Leverages MAPS Platform Against Pneumococcal Disease 

Affinivax announced positive preclinical data from its study evaluating whether incorporating novel pneumococcal fusion protein SPP2 with its vaccine candidate AFX3772 would deliver enhanced protection versus serotype 3 invasive pneumococcal disease. 

The company utilized its MAPS technology platform to engineer a multivalent vaccine by affinity-linking antigens from the target pathogen Streptococcus pneumoniae. SPP2 was added into a MAPS vaccine candidate with more than 30 serotypes, thus creating highly potent antibodies against the toxin. Testing on mouse models, researchers observed that protection was only achieved by those that were given the MAPS vaccine candidate.  

"The MAPS platform offers the possibility of engineering next generation pneumococcal vaccines that can be broadly effective against Streptococcus pneumoniae. These data strongly support a vaccine approach that includes both pneumococcal polysaccharides and conserved pneumococcal proteins to overcome the resistance of serotype 3 to traditional conjugate vaccines," Gilles Besin, Ph.D., vice president and head of discovery research at Affinivax stated. 

Results will be presented at the 12th International Symposium on Pneumococci and Pneumococcal Diseases, June 19 to 23 in Toronto. 

Ocugen and Bharat Biotech's COVID-19 Vaccine Shines in Children

Ocugen announced positive pediatric Phase II/III study results for its COVID-19 vaccine Covaxin (BBV152) in children ages 2 to 18. Covaxin, developed alongside partner Bharat Biotech International, was being evaluated for reactogenicity and immunogenicity. 

"We have now achieved our goal of developing a safe and efficacious COVID-19 vaccine for adults and children, for primary immunization and booster doses, making Covaxin a universal vaccine. It has proven to be a highly safe vaccine based on data from more than 50 million doses administered to children in India," Dr. Krishna Ella, chairman and managing director of Bharat Biotech, commented. 

The open-label, non-randomized trial was conducted in six hospitals in India and involved 526 healthy children. Details of the study are published in The Lancet Infectious Diseases. 

Covaxin so far has an emergency use listing from the World Health Organization. It can be given to adults and children alike. 

https://www.biospace.com/article/positive-updates-in-vaccine-development-for-infectious-diseases/

FDA, HHS Sued by Doctors Over Drug Ivermectin

 Earlier this month, three physicians filed a lawsuit against the Department of Health and Human Services (HHS), HHS Secretary Xavier Becerra, the U.S. Food and Drug Administration, and FDA Commissioner Robert M. Califf in a Texas court. They allege the FDA acted outside its authority and “illegally interfered with their ability to practice medicine” by discouraging the use of ivermectin to treat COVID-19. The physicians are Dr. Robert L. Apter, M.D., Dr. Mary Talley Bowden, M.D. and Dr. Paul E. Marik, MBBCh, MMed.

Bowden is an ear, nose and throat specialist in the Houston area. Marik is an internist and critical care physician board-certified in the U.S., Britain, Canada and South Africa. Apter is licensed to practice medicine in Arkansas and Washington.

The complaint argues that the FDA approved ivermectin for human use in 1996 for several diseases, but after the beginning of the COVID-19 pandemic, the regulator published documents and social media posts saying the drug was dangerous for use with people. That’s something of an oversimplification, in that there were well-reported cases of people using a veterinary-grade version of the drug to self-treat COVID-19.

Ivermectin is approved by the FDA to treat intestinal strongyloidiasis and onchocerciasis, both caused by parasitic worms. The drug is also approved for veterinary use to prevent heartworm and other parasites, but these are different products and are not safe for people.

Ivermectin does have anti-inflammatory properties but is not generally classified as an anti-viral medication. It has also been approved for use as a topical treatment for head lice. Because of its anti-inflammatory properties and because it was cheap and available, some researchers and physicians around the world began using or testing it to treat COVID-19. Some early studies suggested it was helpful, but others did not, with some even suggesting it made the disease worse.

The drug became a political flashpoint as former President Donald Trump recommended it, as well as malaria drug hydroxychloroquine and other unproven approaches such as light therapy. Ivermectin gained a fervent following by Trump supporters and similar politicians, such as Rep. Marjorie Taylor Green (R-Ga.), who tweeted in December 2020, "Ivermectin, monoclonal antibodies & other treatments are saving lives."

In the spring of 2021, the FDA launched an ongoing webpage titled, “Why You Should Not Use Ivermectin to Treat or Prevent COVID-19.” There were four primary points: one, it is not approved for COVID-19 in humans and is not an anti-viral drug; two, taking large doses is dangerous and can cause serious health issues; third, if you have the drug via prescription for an FDA-approved use, get it from a legitimate source and take as prescribed; and four, don’t use drugs intended for animals.

In March 2021, the World Health Organization reported that evidence on ivermectin’s use against COVID-19 was inconclusive and recommended it only be used to treat the disease within clinical trials. A study published in The New England Journal of Medicine in May concluded that “The efficacy of ivermectin in preventing hospitalization or extended observation in an emergency setting among outpatients with acutely symptomatic coronavirus disease 2019 (Covid-19), the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), is unclear.” The authors based it on a randomized, control trial of 3,515 patients, 679 who received ivermectin, 679 who received a placebo and 2,157 who received something else. Patients receiving ivermectin did not have a lower incidence of medical admission to a hospital from disease progression.

In a press release, Bowden said, “Since the pandemic began, I have had one mission - help my patients. I provided access to testing when testing was hard to find. I provided treatment when other doctors told my patients to stay home. I have kept over 3,900 patients out of the hospital, but it hasn’t been easy. Sadly, fighting the system has been a much bigger challenge than fighting the disease. Despite my excellent track record treating COVID patients, the FDA’s smear campaign against ivermectin continues to be a daily hurdle to overcome. I am fighting back - the public needs to understand what the FDA has done is illegal, and I hope this suit will prevent them from continuing to interfere in the doctor-patient relationship.”

Marik, whose degrees (MBBch, MMed) are from the University of the Witwatersrand, Johannesburg, South Africa, stated, “The FDA’s public statements on ivermectin have been misleading and raised unwarranted concern over a critical drug in preventing and treating COVID-19. The agency felt compelled to use language to discourage any discourse and interest in using ivermectin as a front-line treatment of COVID-19. To do this is to ignore both statutory limits on the FDA’s authority and the significant body of scientific evidence from peer-reviewed research, over 80 medical trials, and results from ivermectin’s use in medical settings worldwide, showing the safe and effective use of the drug in fighting COVID-19.”

The Texas Department of State Health Services had issued poison warnings about the drug. In 2020 the Texas State Board of Pharmacy also tried to prohibit prescriptions for hydroxychloroquine dispensed without a diagnosis, but that only lasted six weeks.

Apter indicates she is being investigated by three state medical boards, “each threatening my medical license based on complaints from pharmacists that I have prescribed ivermectin for COVID-19. In all these cases the patients did very well.”

Bowden has received complaints about her use of ivermectin as well.

Marik has a reputation for being outspoken in a number of areas. In a January 2017 Letter to the Editor at Emergency Medicine News titled, “Dr. Marik’s Views Should Not be Taken Serious,” Dr. Anthony O. Cruz, M.D., a physician with Henry Ford Hospital in Detroit, responded to an article by Marik, saying, “…I was stunned by the overtly contrary perspectives presented in this article…. This is especially true for those who are, like I was, not entirely familiar with the author and his reputation as an outspoken skeptic. This article [“Humans Are Not Yeast”] flies in the face of our current mainstream understanding of pathophysiology with respect to acidosis, lactate physiology, and oxygen utilization dynamics, and delivers harsh criticism of sepsis treatment strategies.”

The lawsuit is being represented by Boyden Gray, an attorney who worked for the Reagan and George H.W. Bush administrations and served as the U.S. Ambassador to the European Union during the George W. Bush administration.

https://www.biospace.com/article/fda-sued-by-doctors-over-their-use-of-ivermectin-for-covid-19/

Rain Targets Normal p53 Expression with Possible Pan-Cancer Therapeutic

 Rather than target mutated p53, Rain Therapeutics is looking at normal p53 expression as part of its novel mouse double minute 2 homolog (MDM2) inhibitor therapy. In the coming 12 months, Rain expects to have an interim readout for a Phase II study of its liposarcoma therapy, called milademetan (Rain-32), and a pivotal readout for its Phase III trial of the same compound.

BioSpace caught up with Robert Doebele, M.D, Ph.D., Rain's president, CSO and co-founder, soon after the company’s three presentations at the recent American Society of Clinical Oncology (ASCO) annual meeting.

BioSpace (BSP): What is milademetan?

Robert Doebele (RD): Milademetan is an oral, targeted, MDM2 inhibitor that we licensed from Daiichi Sankyo in the fall of 2020. This type of inhibitor is important because it can reactivate the tumor suppressor gene p53. Almost half of all cancers have lost p53 activity through mutation. In fact, it’s the most mutated gene among all cancers, because loss of p53 activity is thought to be critical for cancer formation. We’re not trying to target p53 mutant cancers, though. We’re trying to target the ones that have a normal p53 gene.

BSP: Why are you targeting cancers with normal p53?

RD: We think those are more likely to be susceptible to MDM2 inhibition because we believe MDM2 is the most critical regulator of p53 when it’s not mutated. This protein actually can get rid of p53 by degradation.

BSP: Why are you targeting well-differentiated and dedifferentiated liposarcoma (WD/DDLPS)?

RD: Dedifferentiated liposarcoma (the focus of our phase III trial) is a unique tumor that is 100% MDM2 gene-amplified and almost 100% p53 wild type, so it has the exact genetics we believe are most important for our drug to work. There aren’t a lot of tumor types that have such uniform genetics.

Additionally, both WDLPS and DDLPS have the same genetics. We believe WDLPS evolves into DDLPS as it becomes more aggressive, and they’re often found together in the same tumor. In fact, almost all dedifferentiated tumors have some component of well-differentiated tumors, which argues for relatedness. The patients don’t get two separate cancers in the same spot. They actually may be intermingled in the same tumor.

WDLPS and DDLPS are relatively resistant to chemotherapy and no targeted therapies are approved for these tumors. The two therapies that have been approved have what we believe is very modest progression-free survival, so there is an unmet need. Of the two indications, our focus is on dedifferentiated tumors because those patients more often need systemic therapy and, therefore, have a greater unmet need.

BSP: After a Phase I clinical trial, you announced progression-free survival of 7.4 months. What’s happened since then?

RD: We will have topline data in the first half of 2023 for the MANTRA study, which is a randomized, multicenter Phase III study of milademetan versus trabectedin in patients with DDLPS. It evaluates second-line or greater patients whose cancers progressed after first-line chemotherapy.

Our second trial, MANTRA-2, was launched in 2021. It is a tumor agnostic basket trial targeting the same MDM2 and p53 genetics as the MANTRA trial, but it looks across all solid tumor types. In this trial, the genetics (amenable to milademetan) may be present in a small percentage of all tumor types. We are working with commercial next-generation sequencing companies and local testing labs to identify patients who have evidence of the required genetic features.

We’re excited to think about tumors in a non-siloed way…and target them with a precision oncology strategy.

BSP: Can milademetan be used with checkpoint inhibitors?

RD: We believe that’s an interesting avenue and one that we addressed in our recent ASCO presentation. In January we announced the MANTRA-4 phase I study, which is a combination of our drug, milademetan, plus Roche’s atezolizumab (Tencentriq), an anti-programmed death ligand (anti-PD-L1) immunotherapy, in a different genetic population of patients.

Based on the known toxicity profiles of the two drugs, we do not anticipate overlapping toxicities with the combination and hence are evaluating the safety of the combination in a dose de-escalation design in which milademetan will start at the preferred dose and schedule, and atezolizumab will start at the approved dose. Preclinical data suggest that reactivation of p53 can help sensitize tumors that otherwise are not sensitive to checkpoint inhibition.

BSP: What’s next for the research?

RD: A lot of our focus now is on other indications that have MDM2 dependencies and hunting for other genetic alterations that are predictive of MDM2 dependence and may benefit from milademetan. We’re also trying to identify effective combinations of milademetan and other therapies. Better understanding of which combinations will make the most sense for this MDM2 inhibitor is one of our most active areas of research. We think it may have very exciting potential for bringing milademetan to more patients with a normal p53 gene.

We are trying to be very rational about how we develop this drug, even if that means addressing small indications at first. We want to show proof of concept that inhibiting MDM2 can really shrink tumors or otherwise lead to meaningful clinical benefit for patients. Once we do that, there is a large population of patients who may benefit from this drug.

https://www.biospace.com/article/rain-targets-normal-p53-expression-with-possible-pan-cancer-therapeutic/

CRISPR Therapeutics Eyes Historic First in Gene Therapy

 CRISPR Therapeutics (CRISPR) could be on the cusp of achieving a first in gene therapy, the first company to achieve regulatory approval for a CRISPR-Cas9 program. The company is anticipating the filing of a Biologics License Application for CTX001, a potential cure for transfusion-dependent beta-thalassemia (TDT) and severe sickle cell disease (SCD).

On Tuesday, the Cambridge, MA-based gene editing company hosted an Innovation Day presentation that highlighted its pipeline and the promise that its multiple approaches have in mitigating or even curing different diseases. Chief Executive Officer Samarth Kulkarni said it has been less than 10 years since Jennifer Doudna and Emmanuelle Charpentier first published an article in the journal Science about gene editing technology and less than eight years since CRISPR Therapeutics was founded on that technological promise. Now, the company is on the cusp of vying for potential approval of its CRISPR therapy, he said.

CTX001, also known as exa-cel, is a CRISPR-Cas9-based gene editing therapy for both TDT and SCD. Earlier this month, CRISPR and its partner Vertex Pharmaceuticals released positive data for exa-cel in TDT and SCD. In the first space, data showed that 42 of 44 patients with TDT who received exa-cel remained transfusion free for up to 37.2 months. The two patients who were not transfusion free had 75% and 89% reductions in transfusion volume, respectively, the companies said. In SCD, all 31 patients with disease characterized by recurrent vaso-occlusive crises (VOCs) were free of the issues following treatment with the gene therapy. Data showed the patients had a duration of up to 32.3 months, CRISPR and Vertex reported. The two companies expanded their partnership in this space last year.

“We are extremely excited about exa-cel,” Kulkarni said.

Phuong Khanh (P.K.) Morrow, CRISPR’s new chief medical officer, echoed Kulkarni, saying that she believes exa-cel will be the first CRISPR-Cas9 product approved for both TDT and sickle cell disease. Her prediction comes about a week after an advisory committee with the U.S. Food and Drug Administration recommended approval of a different gene therapy approach for these diseases that were developed by bluebird bio.

In immuno-oncology, CRISPR is also blazing a trail with its approach, particularly with CTX130, a donor-derived gene-edited allogeneic CAR T therapy that targets CD70, which is expressed on various solid tumors and hematologic malignancies. The company is developing the asset for solid tumors, such as renal cell carcinoma, as well as T cell and B cell hematologic cancers. Morrow suggested the positive data the company has seen with CRX130 in both solid and hematologic tumors is “something of the Holy Grail that researchers have been searching for." 

In May, CRISPR presented exciting CTX130 data from two Phase I studies for relapsed or refractory renal cell carcinoma and various subtypes of lymphoma. The company reported positive early signs, including an overall response rate of 71% from patients with T-cell lymphoma. Of those, 29% experienced a complete response, CRISPR said.

In renal cell carcinoma, cancer that expresses high levels of CD70, CTX130 is also showing significant promise, even leading to a complete response in one patient. Renal cell carcinoma represents a high unmet need, with less than 20% of patients surviving beyond five years. About 40% of RCC patients have shown poor response rates to current therapies.

“There is a high potential opportunity with CTX130 because of the CD70 expression in RCC,” Morrow said.

Beyond those two assets, CRISPR is also advancing other therapeutics. The company is also developing VCTX210, a potential treatment for type 1 diabetes that is being co-developed with ViaCyte. VCTX210 is an allogeneic, gene-edited, stem cell-derived therapy designed to generate pancreatic cells that can evade recognition by the immune system, which would otherwise destroy them. Earlier this year, the companies dosed the first patient in a Phase I study. As BioSpace previously reported, the goal is for the cell line to be differentiated into pancreatic endoderm cells, generating glucose-responsive insulin-secreting cells in the patient. It is expected that about 10 patients will be included in the study. Data is anticipated by the end of the year.

While those programs for CRISPR Therapeutics stand out, Kulkarni said the company sees significant potential with its total pipeline, with a chance to delve into multiple disease indications and potentially bring new treatment options to patients.

“We’re very excited about the potential,” he said.

https://www.biospace.com/article/crispr-eyes-historic-first-in-gene-therapy/

Ocugen Publishes Positive Results of COVID-19 Vaccine Trial for Children 2-18

 Ocugen, Inc. (NASDAQ: OCGN), a biotechnology company focused on discovering, developing, and commercializing novel gene and cell therapies, biologicals, and vaccines, today announced the publication of positive pediatric Phase 2/3 study results in children aged 2–18 years for the COVID-19 vaccine COVAXIN™ (BBV152) in The Lancet Infectious Diseases (“The Lancet”). COVAXIN™ is developed and manufactured by Ocugen’s partner Bharat Biotech International Limited (“Bharat Biotech”), a global leader in vaccine innovation based in Hyderabad, India, and is under clinical investigation by Ocugen in the United States for use in adults aged 18 years and older.

The Lancet article, entitled “Immunogenicity and reactogenicity of an inactivated SARS-CoV-2 vaccine (BBV152) in children aged 2–18 years: interim data from an open-label, non-randomised, age de-escalation phase 2/3 study,” which was authored by Dr. Krishna Mohan Vadrevu, Siddharth Reddy, MSc, and others, was published on June 16, 2022.

Ocugen has commercial rights for COVAXIN™ throughout North America and COVAXIN™ has emergency use authorization in Mexico for adults. Ocugen is continuing to explore pediatric emergency use authorization in Mexico. This data demonstrates that the same dose is effective in both pediatrics and adults (ages two and older) and would be an ideal option as the majority of Americans are looking for traditional vaccine options. Ocugen is continuing its effort to bring this vaccine to the North American Market.

https://finance.yahoo.com/news/ocugen-announces-publication-positive-results-110000976.html

Acer, Relief get FDA Complete Response for urea cycle disorder med

 Citing the need to inspect a third-party contract packaging manufacturer, the U.S. Food and Drug Administration (FDA) has issued a Complete Response Letter (CRL)

The FDA has not raised any approvability concerns related to the efficacy, safety or
pharmacokinetics of ACER-001

https://finance.yahoo.com/news/acer-therapeutics-relief-therapeutics-announce-123000980.html