On December 21, 2023 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS’’ or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) for SLS009, the Company’s novel and highly selective CDK9 inhibitor, for the treatment of relapsed/refractory (r/r) Peripheral T-cell Lymphomas (PTCL) (Press release, Sellas Life Sciences, DEC 21, 2023, View Source [SID1234638754]).

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"We are delighted to announce the FDA’s granting of ODD for SLS009, marking another significant milestone following the recent Fast Track Designation by the FDA for PTCL," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "In the recently completed dose-escalation portion of the Phase 1 trial in r/r hematological malignancies, SLS009 achieved clinical responses in PTCL including two patients reaching complete response. We are excited to see a favorable safety profile, strong initial efficacy signals, and evidence of anti-tumor activity across the Phase 1 study as well as the ongoing Phase 2 studies. With both designations in hand, we look forward to advancing the development of SLS009 and continuing to work closely with regulators with the goal of delivering this treatment to those who may benefit from it."

As it relates to PTCL, SLS009 is currently being evaluated in a Phase 1b/2 trial in patients with r/r PTCL. The open-label, single-arm study will enroll up to 95 patients to evaluate safety and efficacy and, based on the results, may serve as a registrational study. This initial PTCL study is fully funded by GenFleet Therapeutics, Inc. and is being conducted in China.

In the recently completed dose-escalation portion of the Phase 1 trial in r/r hematological malignancies, SLS009 demonstrated a favorable safety profile and promising clinical efficacy. Complete or partial responses were observed in patients with acute myeloid leukemia as well as lymphoma, including four PTCL patients (36.4%) who achieved clinical responses with one patient with complete metabolic response who is continuing treatment for over 62 weeks, and another patient with complete response by CT scan who is continuing treatment for over 24 weeks. The current standard of care for r/r PTCL, belinostat, an HDAC inhibitor, showed in its pivotal Phase 2 study a 25.8% response rate in a similar patient population to that in the SLS009 Phase 1 clinical trial. The patients who achieved complete response in the SLS009 study were previously treated with regimens containing an HDAC inhibitor.

The FDA’s Office of Orphan Products Development grants ODD status to drugs and biologics intended for the safe and effective treatment, diagnosis or prevention of rare diseases or conditions affecting fewer than 200,000 people in the United States. ODD provides benefits to drug developers designed to support the development of drugs and biologics for small patient populations with unmet medical needs. These benefits include assistance in the drug development process, tax credits for qualified clinical costs, exemptions from certain FDA fees and seven years of marketing exclusivity.

On December 21, 2023 Sanofi reported that it is discontinuing the global clinical development program of tusamitamab ravtansine (Press release, Sanofi, DEC 21, 2023, View Source [SID1234638753]). The decision is based on the outcome of a prespecified interim analysis of the Phase 3 CARMEN-LC03 trial evaluating tusamitamab ravtansine as monotherapy compared to docetaxel in previously treated patients with metastatic non-squamous (NSq) non-small cell lung cancer (NSCLC) whose tumors express high levels of carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) (Press release, Sanofi, DEC 21, 2023, View Source [SID1234638753]).

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An Independent Data Monitoring Committee (IDMC) found that tusamitamab ravtansine as a monotherapy did not meet its dual primary endpoint of progression-free survival (PFS) compared to docetaxel. Despite an improved overall survival (OS) trend, termination of the program was based on non-improvement in PFS at the final analysis. Tusamitamab ravtansine had a similar safety profile as previously presented with a lower incidence of various important clinical categories of adverse events versus docetaxel. Trial participants will have the option to stay on their current therapy if they are benefitting, as deemed by their provider, or to transition to an appropriate standard-of-care therapy.

Sanofi will continue exploring the potential of antibody tusamitamab-based ADCs and CEACAM5 research in several types of cancer.

Dietmar Berger
Chief Medical Officer and Head of Development
"Our team is grateful to the patients, families and healthcare professionals involved in the tusamitamab ravtansine development program. Although the results are not what we hoped for, our research and work to advance potentially transformative therapies in areas of high unmet need for people living with cancer will not stop. We will continue to explore the potential of CEACAM5 as a biomarker in cancer types where it is highly expressed."

CEACAM5 is a member of the CEACAM family of 12 glycoproteins and may drive cell adhesion and migration, as well as inhibit apoptosis, and may be overexpressed in many different cancer types.

About the CARMEN-LC03 Trial
CARMEN-LC03 was a randomized, open-label Phase 3 study evaluating tusamitamab ravtansine as monotherapy compared to docetaxel in patients with metastatic NSq NSCLC and high CEACAM5 expression. The dual primary endpoints of CARMEN-LC03 were progression-free survival and overall survival. Secondary endpoints included objective response rate, health-related quality of life, safety and duration of response.

On December 21, 2023 Quest Diagnostics Incorporated (NYSE: DGX), the nation’s leading provider of diagnostic information services, reported that Jim Davis, Chairman, CEO and President, and Sam Samad, Executive Vice President and Chief Financial Officer, will speak on the company’s strategy, performance, and the latest market developments and trends during a fireside chat at the 42nd Annual J.P. Morgan Healthcare Conference in San Francisco on Tuesday, January 9, 2024, at 6:45 p.m. Eastern Time (Press release, Quest Diagnostics, DEC 21, 2023, View Source [SID1234638752]).

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The fireside chat and Q&A session will be webcast live during the conference and will be available on the company’s investor relations page which can be accessed at ir.QuestDiagnostics.com. In addition, the archived webcast will be available within 24 hours after the conclusion of the live event and will remain available until February 8, 2024.

On December 21, 2023 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that a Marketing Authorization Application (MAA) was submitted yesterday to the Medicines and Healthcare Products Regulatory Agency (MHRA) in the UK for DCVax-L for glioblastoma brain cancer (Press release, Northwest Biotherapeutics, DEC 21, 2023, View Source [SID1234638751]).

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The MAA seeks approval for commercialization of DCVax-L for both newly diagnosed and recurrent glioblastoma (GBM). The application also requests to be considered under the MHRA’s rapid 150-day review pathway, which the agency has established for new medicines for serious unmet medical needs.

"We are very excited to reach this important milestone as the culmination of more than 20 years of research and clinical development," commented Linda Powers, Company CEO. "We are extremely grateful to all of the parties who have made this possible, including the patients, the investigators and the shareholders whose patience and support have been invaluable. We believe DCVax-L can offer a much needed new treatment option for GBM patients, both alone and in combination with other treatment agents. We look forward to bringing the treatment to as many patients as possible, including in community settings where most patients are treated."

GBM is the most lethal and most common form of primary brain cancer. Despite well over 400 clinical trials of a wide range of treatment agents, patient survival in newly diagnosed GBM is only 15-17 months and has not meaningfully improved in 20 years; survival in recurrent GBM is only 6-8 months and has not improved in 30 years.

The Company’s international Phase III trial demonstrated a statistically significant and clinically meaningful extension of median survival in both newly diagnosed and recurrent GBM in patients treated with DCVax-L compared with independently selected, matched, contemporaneous, pre-specified external controls. The trial also demonstrated more than doubling of the percentage of patients alive at 5 years in newly diagnosed GBM, and more than doubling of patients alive at 3 years after tumor recurrence in recurrent GBM patients, although the numbers of patients available for comparison at late time points was small, especially in the external control populations.

One of the key factors making GBM so difficult to treat is that it is an extremely heterogeneous tumor. "Accumulating evidence suggests that intratumor heterogeneity likely is the key to understanding treatment failure" in GBM (Sottoriva, PNAS, 2013). Another key challenge is that as GBM develops, it induces an immunosuppressive microenvironment which compounds the difficulty of mounting an effective immune response against the tumor – especially within the central nervous system, which is an immune privileged space behind the blood brain barrier.
DCVax-L is designed to address both of these key challenges.

As the Company previously reported, proteomic studies have demonstrated that a single tumor lysate sample contained tens of thousands of different peptides and, out of this pool, the dendritic cells selected, processed and presented over 600 different peptides (tumor targets) to T cells. T cell studies (TCR sequencing and T cell clonal expansion assays) analyzing the breadth and strength of T cell response following DCVax-L treatment have found extensive responses, including clonal expansion of up to 800 T cell clones at month 4 and up to 1200 T cell clones at month 8 in the samples studied. Each T cell clone focuses on a particular and distinct target. In individuals not being treated with the vaccine, only 2 – 20 new T cells clones are seen between month 4 and month 8.

The results of these proteomic, T cell and other studies provide support for what the Company believes to be the mechanism of action of DCVax-L: i.e., mobilizing a broad spectrum and strong de novo T cell response that addresses the extensive heterogeneity of GBM and overcomes the immunosuppressive microenvironment around the tumor.

The Company believes that this mechanism of action will be applicable for most types of solid tumors. Solid tumors comprise approximately 90% of all cancers, and a key difficulty that other treatment approaches have encountered with solid tumors is their heterogeneity.

The Company has already had positive results with DCVax-L in some compassionate use cases with other diverse solid tumors. The Company looks forward to building on its experience with DCVax-L in GBM and the compassionate use cases to address a wide range of other operable solid tumors.

The Company also had positive results in its Phase 1 trial of DCVax-Direct, in which more than a dozen diverse types of inoperable solid tumors were treated. DCVax-Direct involves essentially the same mechanism of action as DCVax-L, except that the tumor target proteins are taken up by the dendritic cells in situ in the tumor following intra-tumoral injection, rather than from tumor lysate from a surgically resected tumor tissue sample. The Company looks forward to resuming its clinical development of DCVax-Direct for a wide range of inoperable solid tumors.

For the GBM MAA, the Company anticipates that the review process will be a period of intensive and extensive further work involving responding to questions and requests for further information by the regulatory authority as well as preparing for and undergoing detailed inspections of the contract research organizations (CROs) that managed the trial, the Sponsor, the Trial Master File, a number of individual trial sites selected by the regulator from among the 94 sites that participated in the trial, the GMP facility and manufacturing information.

On December 21, 2023 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported that Gilead Sciences (‘Gilead’) has purchased 15 million shares of HOOKIPA’s common stock for approximately $21.25 million, at a price of $1.4167 per share (Press release, Hookipa Biotech, DEC 21, 2023, View Source [SID1234638750]).

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In addition, HOOKIPA has the right, subject to certain terms and conditions, to sell an additional approximately $8.75 million of common stock to Gilead as pro-rata participation in potential future equity raises. The agreement with Gilead replaces the stock purchase agreement that Hookipa entered into with Gilead in 2022.

"We have a tremendous partnership with Gilead, who have been incredible believers in our arenavirus platform since our initial collaboration and license agreement began more than five years ago," said Joern Aldag, Chief Executive Officer at HOOKIPA. "Together, we have made meaningful progress to find a potential functional cure for HIV. Most recently, we received clearance from the U.S. Food and Drug Administration of our Investigational New Drug application for HB-500 and are excited to begin our Phase 1 trial in the first half of next year. We are excited to continue our relationship with Gilead, and we are collectively optimistic about the potential of our partnership to benefit patients."

The transaction closed on December 20, 2023. Following the completion of the stock purchase, Gilead’s ownership in HOOKIPA increased to 18,759,465 shares, or approximately 19.4% of HOOKIPA’s outstanding shares of Common Stock.

HB-500 is an alternating, 2-vector arenaviral therapeutic vaccine that is being evaluated as part of a potential curative regimen for HIV. One vector is based on lymphocytic choriomeningitis virus (LCMV) as its arenaviral backbone; another vector is based on Pichinde virus (PICV). Both encode the same HIV antigens. The alternating 2-vector approach is designed to further focus the immune response against the target antigen.

HB-500 is one of two separate development programs in HOOKIPA’s collaboration and license agreement with Gilead. HOOKIPA is responsible for advancing the HIV program through the completion of a Phase 1b clinical trial. Gilead has the exclusive right to assume further development of the program thereafter.

For further details, refer to the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission (the ‘SEC’) on December 21, 2023.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. Any offering of the shares of common stock described above under the resale registration statement will only be by means of a prospectus.