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Friday, September 2, 2022

October 28 Review Set for Y-mAbs' Refiling For Omburtamab

The Oncologic Drugs Advisory Committee (ODAC) of the U.S. Food and Drug Administration (FDA) has been scheduled for October 28, 2022 to review Y-mAbs Therapeutics’ 

 Biological License Application (BLA) for its product candidate, OMBLASTYS (omburtamab) for pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma.

The company resubmitted the Biologics application in the month of March 2022.

The regulatory agency has accepted the BLA under priority review and assigned Prescription Drug User Fee Act (PDUFA) goal date of November 30, 2022.

Thomas Gad, President, and Interim Chief Executive Officer, commented: "We look forward to the October 28, 2022 meeting with the Advisory Committee, as well as to continuing our dialogue with the FDA about OMBLASTYS and the important data, which we believe supports approval. This is another key step towards providing a potential treatment for pediatric patients with CNS/leptomeningeal metastasis from neuroblastoma."

Omburtamab was developed by researchers at Memorial Sloan Kettering Cancer Center (MSK) and licensed to Y-mAbs.

Y-mAbs is a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic cancer products.

https://www.benzinga.com/general/biotech/22/09/28727181/fda-advisory-committee-scheduled-for-october-28-2022-to-review-y-mabs-refiling-for-omburtamab

Raymond James Initiates AnaptysBio With ~42% Upside, Despite Trial Setback

 

  • Raymond James initiated coverage on AnaptysBio Inc  with an Outperform rating and a $35 price target.
  • The analyst has a positive outlook on the lead asset imsidolimab in generalized pustular psoriasis (60% PoS — top-line data in 4Q23).
  • In addition to imsidolimab, AnaptysBio is developing PD-1 agonist rosnilimab in alopecia areata (AA), and the data from Phase 2 AZURE study is expected in 1Q23. 
  • AnaptysBio’s another checkpoint agonist (ANB032 targeting BTLA) completed Phase 1 in healthy volunteers, and Phase 2 development could start as soon as 4Q22. 
  • The analyst says that though ANB032 is not captured in the model, for now, they note some recent interest from big pharma in checkpoint agonists for autoimmune indications, and Gilead Sciences Inc  acquired private MiroBio for $405 million.
  • MiroBio’s lead asset MB272 (BTLA agonist) is somewhat behind ANB032, while MB151 (PD-1 agonist) is still in preclinical development. 
  • According to the analyst, investors may remain on the sidelines due to the binary readout for imsidolimab in hidradenitis suppurativa (HS) while the interest for checkpoint agonists is rising.

PolyPid's Lead Program Flunks Abdominal Surgery Study

 

  • PolyPid Ltd (NASDAQ: PYPD) shares lost almost 80% after announcing topline results from the SHIELD I Phase 3 study of D-PLEX100 for preventing surgical site infections (SSIs) in abdominal surgery.

  • D-PLEX100, compared to SoC alone, did not achieve statistical significance on the key secondary endpoint evaluating SSI events within 30 days post-abdominal index surgery.

  • In the Intent to Treat (ITT) population, the local administration of D-PLEX100 and SoC (n=485) resulted in a decrease in SSIs and mortality of 23% compared to SoC alone.

  • Within the first 30 days post-surgery, there were 15 deaths in the SoC arm compared to 11 in the D-PLEX100 arm.

  • In a pre-specified subgroup ITT analysis requested by FDA, D-PLEX100 resulted in a statistically significant reduction of 54% on the primary endpoint compared to SoC alone.

  • The SHIELD I study is designed to demonstrate at least a 50% reduction in incisional SSIs in the D-PLEX100 arm compared to the control arm.

  • Within the first 30 days post-surgery, SSIs decreased from 8.5% in the SoC treatment arm to 4.2% in the D-PLEX100 treatment arm.

  • The independent Data Safety Monitoring Board raised no safety concerns in SHIELD I.

  • The company's second Phase 3 trial of D-PLEX100 for preventing SSIs in abdominal surgery, SHIELD II, is ongoing and has enrolled over 200 subjects.

  • In May, the independent Data Safety Monitoring Board (DSMB) recommended concluding enrollment in PolyPid SHIELD I Phase 3 study of D-PLEX100.

Opening Door to New Class of Melanoma Therapeutics

 Investigators at Sanford Burnham Prebys found that inhibiting a key metabolic enzyme kills melanoma cells and halts tumor growth, opening the door for a new class of drugs to treat melanoma. 

"Rarely do we find tumor-specific pathways that signify a tumor type," Ze'ev Ronai, Ph.D., professor and director of the National Cancer Institute (NCI)-designated Cancer Center at Sanford Burnham Prebys, told BioSpace. "Here, the finding of GCDH as a melanoma-specific gene to which the cancer is dedicated to offers novel paths for understanding what makes melanoma unique compared with other tumors, and how this can be exploited therapeutically."

The authors write that melanoma has an “addiction to the mitochondrial protein glutaryl-CoA dehydrogenase (GCDH), which functions in lysine metabolism and controls protein glutarylation.”

When they inhibited the enzyme, it led to changes in a key protein, called NRF2, which acquires its ability to suppress cancer. GCDH plays a key role in metabolizing lysine and tryptophan, which are essential amino acids. The Ronai laboratory assayed melanoma cells to determine how they generate energy from lysine. They found that GCDH was crucial.

“Melanoma cells ‘eat’ lysine and tryptophan to produce energy,” said Sachin Verma, Ph.D., a postdoctoral researcher in the Ronai lab and first author of the study.

But using energy from the pathway demands that cancer cells control toxic waste produced during the process. There are six steps in the process, and Verma noted, “We thought the cells would need all six enzymes. But it turns out only one of these enzymes is crucial, GCDH. Melanoma cells cannot survive without the GCDH portion of the pathway.”

By inhibiting GCDH in laboratory animals, they were able to suppress the progression of melanoma. Earlier research demonstrated that NRF2 could drive and repress cancer, but they didn’t know how to shift NRF2 from driving cancer to stopping cancer. 

“Our current study identifies the answer,” Ronai noted.

In their research, the animals who did not have GCDH were essentially normal but could not tolerate a high-protein diet. Melanoma patients’ tumors are typically low in GCDH. Because GCDH plays a role in protein processing, the researchers think GCDH-poor tumors might be susceptible to high-protein foods. This suggests the possibility of dietary treatment. Also, decreasing GCDH tumor levels with drugs may be enhanced by specific protein diets.

They note that because normal cells that lack GCDH are mostly unaffected, drugs that inhibit GCDH would likely be specific to melanoma cells. Ronai’s laboratory is now collaborating with the Conrad Prebys Center for Chemical Genomics at Sanford Burnham Prebys to identify potential small molecule GCDH inhibitors.

“In the study, we used genetic approaches to inhibit GCDH, which provide the proof of concept to search for small molecules inhibitors,” Verma said. “Indeed, we are actively searching for potential drugs that could inhibit GCDH, which would be candidates for novel melanoma therapies.”

Ronai told BioSpace, "We will identify small molecules that can selectively target GCDH, an effort we undertake with our drug discovery center (The Prebys Center) at Sanford Burnham Prebys. The possible use of specific diets or immune checkpoint therapy with GCDH inhibition will also be examined."

The research was published in Nature Cell Biology.

Meanwhile, other companies are conducting clinical studies with other compounds to treat melanoma. 

AIM ImmunoTech and Roswell Park Comprehensive Cancer Center announced on Aug. 30 that they had initiated patient enrollment in a Phase II trial in patients with primary PD-1/PD-L1 resistant melanoma. The study will evaluate a type-1 polarized dendritic cell vaccine in combination with a tumor-selective chemokine modulation made up of interferon-alpha 2b, Ampligen (rintatolimod) and Celecoxib. Ampligen is AIM’s dsRNA product candidate.

On Aug. 23, Immatics treated the first patient in its Phase Ib expansion cohort C of IMA203CD8, its second-generation TCR-T monotherapy where a proprietary CD8aß co-receptor is added to PRAME-specific IMA203 T cells.

PRAME refers to a melanoma antigen preferentially expressed in tumors. Interim data from the company’s Phase Ia trial demonstrated a 50% objective response rate in various solid tumors, including melanoma, head and neck cancer, uveal melanoma and synovial sarcoma.

https://www.biospace.com/article/opening-the-door-to-potential-new-therapies-for-melanoma/