On October 22, 2024 CEL-SCI Corporation (NYSE American: CVM) reported the potential positive impact on the clinical development of its immunotherapy Multikine (Leukocyte Interleukin, Injection)* resulting from a recent U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) meeting, a public forum (Press release, Cel-Sci, OCT 22, 2024, View Source [SID1234647321]).

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FDA advisory committees provide independent expert advice to the FDA on the safety and effectiveness of new and marketed drugs and help the agency make sound and informed decisions. Advisory committees make non-binding recommendations to the FDA, which generally follows the recommendations but is not legally bound to do so.

The September 27, 2024 ODAC meeting evaluated the use of checkpoint inhibitors on patients with various cancers. PD-L1 is the biomarker most often used for patient selection for checkpoint inhibitors, the most successful class of cancer drugs including Keytruda and Opdivo. The FDA sought the ODAC’s opinion on the following:

adequacy of PD-L1 expression as a predictive biomarker for patient selection in this patient population
differing risk-benefit assessments in different subpopulations defined by PD-L1 expression
adequacy of the cumulative data to restrict the approvals of immune checkpoint inhibitors based on PD-L1 expression
Following a thorough analysis of peer-reviewed published data, the panel of experts on the ODAC voted 10-2 and 11–1 against the risk-benefit profile for PD-L1 inhibitors in various cancers in two separate votes. Most ODAC members expressed concerns about the lack of benefit demonstrated for patients with low PD-L1 expression, while some members pointed to evidence that the use of the immune checkpoint inhibitors may add unnecessary toxicities for patients while also increasing financial burdens on patients.

Checkpoint inhibitors were an estimated $48 billion global market in 2023, with PD-L1 inhibitors representing 73% of the market. Current labeling for approved checkpoint inhibitors in the indications evaluated by the FDA’s ODAC include broad approvals for all patients, regardless of PD-L1 expression.

"The FDA advisory committee’s findings and public statement on the risk-benefit of checkpoint inhibitors based on PD-L1 expression is potentially a turning point in cancer treatment, pointing to a major treatment gap in low and negative PD-L1 patients. While the approved blockbuster checkpoint inhibitors, including Keytruda which is expected to be the biggest selling drug in 2024, work well in high PD-L1 expressing patients, to our knowledge, Multikine is the only immunotherapy that is targeted to and has shown survival benefit in the low and negative PD-L1 population. CEL-SCI has already identified in our prior study low PD-L1 expression as a predictive biomarker, representing about 70% of head and neck cancer patients, which will be used as a selection criterion for our upcoming FDA confirmatory Registration Study of Multikine in the treatment of treatment-naïve resectable locally advanced head and neck cancer," stated CEL-SCI CEO Geert Kersten.

"The FDA’s ODAC decision further supports our belief that Multikine holds strong potential in treating patients across a wider range of solid tumor cancer indications alone and in combination regimens," Kersten concluded.

On October 22, 2024 Oncodesign Precision Medicine (OPM) (ISIN: FR001400CM63; Mnemonic: ALOPM), a biopharmaceutical company specializing in precision medicine for the treatment of resistant and metastatic cancers, reported details of the final results of its Phase 1 clinical trial with OPM-101, its RIPK2 inhibitor and drug candidate administered orally to healthy volunteers, first reported on July 16, 2024 (Press release, Oncodesign Precision Medicine, OCT 22, 2024, View Source [SID1234647320]). This clinical trial began in February 2023, the database was frozen in June 2024, and the full results and final study report became available, as scheduled in the study timetable, in October 2024.

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OPM-101 is an experimental, powerful and selective small molecule inhibitor of the RIPK2 kinase. OPM-101 is designed to modulate the pro-inflammatory signal transmission pathway of this kinase, which is responsible for the development of inflammatory diseases, and has the potential to treat diseases in the fields of IBD (Chronic Inflammatory Bowel Disease) and immuno-oncology.

This randomized, double-blind, placebo-controlled phase 1 study was designed to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of OPM-101 (EudraCT: 2022-003122-50) in 104 healthy volunteers:

– In the SAD part of the trial, 72 HV (mean age = 34 years) received a single oral dose of placebo or 5, 20, 60, 150, 300, 600 or 1,000 mg of OPM-101, with one cohort dedicated to the high-fat meal effect and another to the gender effect, also receiving 150mg.

– In the MAD part of the trial, 32 HV (mean age = 36 years) received an oral dose of 75, 150 or 300 mg of OPM-101 or placebo twice daily for 14 consecutive days, including a cohort dedicated to the gender effect, receiving 150mg twice a day.

Safety assessments (physical examination, vital signs, blood tests, ECGs, holters) were performed regularly throughout the trial. In addition, blood samples were collected to measure circulating concentrations of OPM-101 and engagement of RIPK2, the pharmacological target of OPM-101 (measured by inhibition of stimulated TNFα production).

Robust safety data, no toxicity on cardiac parameters

OPM-101 was very well tolerated after administration in SAD and MAD. No severe or serious adverse events were reported, and no volunteer discontinued the study. All treatment-emergent adverse events considered to be at least possibly drug- and study-related were mild to moderate. Fourteen healthy volunteers (13.5%) reported a total of 18 adverse events considered related to study treatment (OPM-101 or placebo). Among them, 12 healthy volunteers (15%) reported a total of 15 adverse events considered to be related to OPM-101, the majority of which were headaches. 80% of these events were mild and 20% moderate. There were no clinically significant changes in safety-related laboratory tests reported during the treatment periods for all OPM-101 dose cohorts included in the analysis, with the exception of one volunteer who received a dose of 150mg twice daily and experienced a moderate (3x normal) increase in ALT (liver enzyme) during MAD, leading to discontinuation of her treatment on the morning of study day 12. In this volunteer, further increases in liver proteins were not observed.

Cardiac function was monitored in detail with daily 12-lead ECGs, particularly at the time of peak circulating concentrations. 24-hour ECG recordings (holters) and cardiac ultrasound were also performed. All these examinations showed normal results, without any relation to circulating OPM-101 concentrations, and without any clinically significant changes. This type of monitoring is common at this stage of development, particularly for kinase inhibitors. The results obtained make OPM-101 a first-rate molecule in this field.

Promising pharmacokinetic and pharmacodynamic results

OPM-101 significantly inhibits the RIPK2 pathway. Target engagement kinetics and pharmacodynamic results showed a fast and marked onset of inhibitory effect, already observed 2-6h after first administration, with maximal inhibition of 90-100%, and minimal inhibition of 65%-85% maintained over 14 days of dose-dependent administration. Inhibition remained marked (50% to 80%) 24 hours after the last administration on day 14 in the MAD part.

The pharmacokinetic parameters of OPM-101 showed consistent results between the SAD and MAD parts, and characteristics suitable for use in patients. OPM-101 is rapidly absorbed, with a Tmax observed between 2-4h, a terminal half-life of around 12h, steady-state reached after 3-4 days and dose-dependent exposure with repeated administration.

On the basis of the PK/PD relationship determined from the results of the MAD part of the study, we anticipate that a very significant target commitment (≥80%) can be achieved and maintained with a residual OPM-101 plasma concentration (Cmin) in the range 150-300 ng/mL. In addition, population pharmacokinetic modelling has enabled us to simulate different dose regimes for a future clinical study, and the target dose could be 150mg twice daily.

OPM and Professor Peyrin-Biroulet, presented the phase 1 results at the United European Gastroenterology Week (UEGW) 2024 held from October 12 to 15, 2024 in Vienna, Austria.

Based on the results presented today, OPM plans to submit a protocol for a phase 1b/2a clinical study in the fourth quarter of 2024.

"We are very pleased with the progress and results of this clinical trial with OPM-101, which provided convincing results for all primary, secondary and exploratory endpoints included in this study," said Philippe Genne, Chief Executive Officer of OPM. "We are pleased to demonstrate the safety of our candidate and the strong pharmacodynamic correlation that exists. High target engagement is demonstrated at tolerated doses of OPM-101 throughout the treatment period. The modulation of TNFα production ex vivo can be considered as a key biomarker of target engagement for future clinical trials. The clinical results reported today not only highlight the consistency with the immunomodulatory effect of OPM-101 observed in preclinical studies, but also validate OPM-101 as a safe and effective inhibitor of the RIPK2 pathway. We are currently in the process of identifying with our scientists and clinicians’ experts the first clinical indication that we will explore in a phase 1b/2a study before the end of the year in order to provide a first clinical proof of concept in a patient population capable of generating significant added value for our asset".

"These complete Phase 1 results confirm and validate OPM-101 as a highly specific, effective and well-tolerated inhibitor of the RIPK2 immune pathway," added Jan Hoflack, Deputy CEO and Chief Scientific Officer of OPM. "The field related to this therapeutic approach is currently booming with new high quality preclinical and clinical scientific publications mentioning a potential role for an inhibitor like OPM-101 in multiple immuno-oncology indications, in addition to the already well-established rational for the treatment of IBD and other inflammatory diseases. Our team is currently working to validate the different therapeutic options available for OPM-101, with the aim of launching a proof-of-concept clinical trial in relevant patients rapidly and efficiently before the end of the year. The current idea of a safe and effective RIPK2 inhibitor like OPM-101 suggests significant potential in both IBD and immuno-oncology, two of today’s largest pharmaceutical markets with significant unmet needs".

On October 22, 2024 AbCellera (Nasdaq: ABCL) reported that executives from the Company will be presenting at the following investor conferences (Press release, AbCellera, OCT 22, 2024, View Source [SID1234647319]):

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Stifel Healthcare Conference on Monday, November 18, 2024, at 8:30 a.m. Pacific Time (11:30 a.m. Eastern Time)
Jefferies London Healthcare Conference on Tuesday, November 19, 2024, at 10:00 a.m. Pacific Time (5:00 p.m. Greenwich Mean Time)

Live audio webcasts of each presentation may be accessed through links that will be posted on AbCellera’s Investor Relations website. Replays of each webcast will be available through the same links following the presentations.

On October 22, 2024 AvenCell Therapeutics, Inc. ("AvenCell"), a leading clinical-stage cell therapy company focused on advancing both autologous and allogeneic switchable CAR-T cell therapies, reported that it has raised $112 million in Series B financing. The financing was led by global life sciences investor Novo Holdings (Press release, AvenCell Therapeutics, OCT 22, 2024, View Source [SID1234647318]). New investors F-Prime Capital, Eight Roads Ventures Japan, Piper Heartland Healthcare Capital and NYBC Ventures also participated in the round alongside founding investor Blackstone Life Sciences. As part of this financing, Michael Bauer, Ph.D., Partner, Venture Investments, Novo Holdings, and Nihal Sinha, MB BChir, Partner, F-Prime Capital will join AvenCell’s Board of Directors.

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This latest financing will support ongoing clinical validation of AvenCell’s proprietary, switchable universal CAR-T cell therapy platform that generates CAR-T cells that can rapidly be turned "Off" and "On" even after they are administered to a patient. The universal platform was developed to more safely and effectively treat a wide range of hematologic malignancies compared to conventional cell therapies. Current clinical assets utilizing AvenCell’s universal platform include AVC-101, a highly-differentiated autologous CAR-T cell candidate, and AVC-201, a CRISPR-engineered allogeneic CAR-T cell candidate. Both products target the antigen CD123 found on most Acute Myeloid Leukemia (AML) cells. The ongoing trials are investigating both products for the treatment of relapsed/refractory AML, which has a high unmet medical need, and very limited treatment options for patients. In addition, AvenCell has several pipeline candidates entering the clinic over the next two years.

"We are excited by the progress of our pipeline and believe our next-generation immunotherapies have the power to address significant unmet patient needs," said Andrew Schiermeier, Ph.D., Chief Executive Officer, AvenCell Therapeutics. "AvenCell is working to transform the standard of care through switchable, adaptable and readily available cell therapy treatments that can better treat a wide range of difficult-to-treat cancer and autoimmune diseases. The support of Novo Holdings and this leading group of new investors will be integral to our ability to progress and bring these therapies to patients."

"AvenCell’s universal switchable technology and CRISPR-engineered allogeneic platforms are first-of-its-kind and represent a step change in the field of cell therapy. Both AVC-101 and AVC-201 have already yielded encouraging safety and efficacy results in early clinical trials in a very difficult to treat disease like AML. Our investment reflects our confidence in these assets and the future of cell therapy, as well as our long-held strategy to support companies transforming care solutions to enhance patient outcomes," said Michael Bauer, Partner, Venture Investments, Novo Holdings.

"AvenCell’s switchable CAR-T platform represents a paradigm shift in cell therapy, offering unprecedented control over treatment dynamics," said Nihal Sinha, MB BChir, Partner at F-Prime Capital. "The ability to modulate CAR-T cell activity post-infusion could address critical safety and efficacy challenges in current therapies. We look forward to supporting AvenCell’s journey in advancing these promising cell therapies through clinical development, with the potential to address significant unmet needs in the treatment landscape."

On October 22, 2024 SFA Therapeutics, Inc., a clinical-stage biopharmaceutical company developing oral small-molecule biosynthetic compounds for the treatment of inflammatory diseases, reported the expansion of its intellectual property in autoimmune disease and hepatocellular carcinoma (Press release, SFA Therapeutics, OCT 22, 2024, View Source [SID1234647317]). SFA Therapeutics has been issued a new patent in the United States (11963938) and has been allowed two patent applications in Canada (2,974,510) and in Korea (10-2017-7023391) with patent coverage through 2036. SFA Therapeutics has also been issued one new patent in Korea (10-2646764) with patent coverage through 2038.

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The United States patent and the allowed Canadian and Korean patent applications protect the short chain fatty acid composition that comprises SFA’s proprietary oral small-molecule biosynthetic compound SFA-001. SFA-001 is a potent immunomodulator being evaluated for the prevention, delay of onset, and treatment of hepatocellular carcinoma. In preclinical studies, SFA-001 demonstrated cytotoxicity against two common human liver cancer cell lines expressing the hepatitis B oncoprotein, HBx. Huh7x and Hep3BX are highly sensitive to SFA-001 without damage to normal liver cells. In 2019, the United States Food and Drug Administration granted an Orphan Drug Designation (ODD) to SFA-001 for the treatment of hepatocellular carcinoma.

The Korean patent protects the short chain fatty acid composition that comprises SFA-002, SFA Therapeutics’ lead candidate and Phase-2 ready potent immunomodulator being evaluated for the treatment of psoriasis. SFA-002 acts on multiple therapeutic pathways with the aim of restoring balance to the immune system. While SFA-002 inhibits pathways of pro-inflammatory cytokines such as IL-17, IL-23, TNF-α, and IFN-y, it also increases Treg differentiation and upregulates the anti-inflammatory cytokine IL-10.

"As SFA’s clinical development progresses, we understand the importance of strengthening our intellectual property portfolio to protect SFA Therapeutics’ proprietary therapeutic candidates," said Dr. Ira Spector, Chief Executive Officer of SFA Therapeutics. "The expansion of our patent portfolio allows us to continue the research and development necessary to bring drug candidates like SFA-001 and SFA-002 through the clinic to patients of autoimmune and inflammatory diseases. This brings the total number of issued and allowed SFA Therapeutics patents to 15, with 33 additional patents pending."

"These patents demonstrate the novel nature of SFA Therapeutics’ platform and drug candidates which are developed by adding disease-specific adjuvants to compounds that are naturally found in the human body," said Dr. Mark Feitelson, Chief Scientific Officer of SFA Therapeutics. "Our therapeutic candidates target multiple pathways in autoimmune and inflammatory conditions, working to inhibit pro-inflammatory cytokines, up-regulate anti-inflammatory targets, and suppress autoimmunity. We believe the intellectual property protected by these patents has the potential to not only manage symptoms from diseases, but to also address the underlying cause of these conditions and prevent or delay their onset."