On December 4, 2024 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ: SONN), a clinical-stage company developing innovative targeted immunotherapeutic drugs, reported the publication of extensive discovery, development and preclinical data on SON-1010 demonstrating its mechanism of action in Frontiers in Immunology (Press release, Sonnet BioTherapeutics, DEC 4, 2024, View Source [SID1234648794]). SON-1010, Sonnet’s lead proprietary drug candidate, combines the Company’s fully human albumin-binding (FHAB) construct with a native single-chain IL-12 sequence to simplify delivery of the cytokine systemically. The paper entitled "SON-1010: An Albumin-binding IL-12 Fusion Protein with Improved Cytokine Half-life Targets Tumors and Enhances Therapeutic Efficacy," details the identification of single-chain variable fragments (scFv) from a human phage display library that bound human, mouse, and cynomolgus macaque serum albumin, both at physiologic and acidic conditions. The composition of matter patent claims on the FHAB domain and SON-1010 fusion protein have been issued in a number of major markets, including but not limited to the U.S., China, Japan, Russia and New Zealand, and expire between 2038 and 2039. Additionally, the Company announced the release of a "What This Means" segment to discuss the publication which is now available here.

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The extensive discovery program included putting the scFv domains through a series of steps to identify strongly binding molecules that bind tightly over a 5.8 to 7.2 pH range and do not interfere with the normal physiology of albumin to bind the neonatal Fc receptor (FcRn). This resulted in having prolonged half-life in serum and binding to SPARC/GP60, which allows albumin to target the tumor microenvironment (TME). A final molecule was selected and a single mutation was introduced that minimizes the potential for immunogenicity. This FHAB domain was characterized, and manufacturing processes were developed to prepare Sonnet’s first drug candidate for the clinic. Once identified, the murine form of mIL12-FHAB was shown to be much more efficient at blocking tumor growth compared to murine IL-12, while stimulating significant and prolonged IFNγ production with minimal toxicity. Biodistribution studies in mice confirmed tumor delivery and toxicological studies in non-human primates allowed the initiation of the clinical trials.

"We are pleased to share these findings, which is the first time we have fully described the extensive research that was required to discover and develop our signature FHAB platform," said Pankaj Mohan, Ph.D., Founder and CEO of Sonnet. "This work lays the foundation for all of the products on our platform that are designed to safely extend the half-life of cytokines and deliver them to the tumor, where they can convert the immunological response from ‘cold’ to ‘hot’ and potentially realize the promise of immunotherapy."

"IL-12 and related compounds have been extensively studied in cancer and immunotherapy indications. However, recombinant interleukins have had limited clinical success owing to their short circulating half-life, inefficient TME targeting, and requirement for frequent dosing, often leading to substantial systemic toxicities," added John Cini, Ph.D. Co-Founder and CSO of Sonnet. "We believe we have addressed these issues with our discovered platform, having utilized a molecule that can be applied in any solid tumor type that concentrates albumin, such as sarcoma, gynecologic, and gastrointestinal cancers. We intend to explore new compounds as well, as funds become available."

The Company is currently conducting a Phase 1 clinical trial of SON-1010 (IL12-FHAB) as a monotherapy in adult patients with advanced solid tumors (SB101; NCT05352750). The Company expects to report safety data from this study in Q4 2024. SON-1010 is being evaluated in an ongoing Phase 1/2a study through a Master Clinical Trial and Supply Agreement, along with ancillary Quality and Safety Agreements, with Roche in combination with atezolizumab (Tecentriq) for the treatment of Platinum-Resistant Ovarian Cancer (PROC).

On December 4, 2024 Nykode Therapeutics ASA (OSE: NYKD), a clinical-stage biopharmaceutical company dedicated to the discovery and development of novel immunotherapies, reported new data from its mRNA-based neoantigen vaccine platform for individualized cancer immunotherapy, presented at the Personalized Cancer Vaccines Summit in Boston (Press release, Nykode Therapeutics, DEC 4, 2024, View Source [SID1234648789]). The findings highlight the platform’s ability to elicit robust and durable immune responses.

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Nykode has previously demonstrated that the neoantigen vaccine induces strong, CD8-biased T cell responses, targeting the majority of the encoded neoantigens. The novel pre-clinical data examines the kinetics of individual neoantigens, showing distinct dose-response patterns. The findings underscore the importance of an optimal vaccination schedule, highlighting differentiated responses to early versus late boost vaccinations.

The vaccine’s ability to provide complete tumor protection with prophylactic administration has been demonstrated. Now, new data reveal that this tumor protection is durable: a single vaccination provided partial long-term protection, while two vaccinations achieved complete and sustained protection at day 90.

"These data reinforce the robust and durable immune responses our neoantigen vaccine generates also in a mRNA format, further validating its potential as a personalized cancer immunotherapy platform," said Agnete Fredriksen, Chief Scientific Officer and Co-founder of Nykode Therapeutics.

Details for the Nykode Therapeutics’ presentation are as follows:

Title: Nykode’s Individualized Cancer Vaccine Approach Across DNA and mRNA

Time & Date: 1:30pm ET, December 4, 2024

The presentation is available on the Nykode website at View Source

About VB10.NEO

VB10.NEO is a proprietary individualized neoantigen vaccine in development for the treatment of locally advanced or metastatic solid tumors. The vaccine is designed to be produced on-demand according to the neoantigen profile of an individual patient. Neoantigens are proteins generated by tumor-specific mutations not present in normal tissues and are thus an attractive target for cancer immunotherapy as they may be recognized as foreign by the immune system. VB10.NEO has been evaluated in multiple indications in two clinical trials. It has been shown to be generally well tolerated and with an ability to generate uniquely broad patient- and tumor-specific long-lasting immune responses.

On December 4, 2024 Flamingo Therapeutics ("Flamingo") reported that an abstract has been selected for presentation at the 66th Annual ASH (Free ASH Whitepaper) Annual Meeting and Exposition, being held in San Diego, CA from December 7-9, 2024 (Press release, Flamingo Therapeutics, DEC 4, 2024, View Source;utm_medium=rss&utm_campaign=flamingo-therapeutics-announces-poster-presentation-on-aml-phase-1-iit-study-at-ash-2024 [SID1234648788]).

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The abstract, selected for a poster presentation, is a Trials-in-Progress presentation of a Phase 1 investigator-initiated study of danvatirsen monotherapy followed by danvatirsen combination with venetoclax in relapsed/refractory AML and intermediate/high risk MDS (NCT05986240). The study is being conducted at Albert Einstein / Montefiore Medical Center in New York City and MD Anderson Cancer Center in Houston.

Poster presentation details are as follows:

Title: "A Phase 1 Study Investigating the Safety and Efficacy of Danvatirsen As Monotherapy Followed by Combination with Venetoclax in Patients with Relapsed/Refractory MDS and AML"
Session Date: Monday, December 9, 2024
Presenting Author: Dr. Aditi Shastri

On December 4, 2024 Corvus Pharmaceuticals, Inc. (NASDAQ: CRVS), a clinical-stage biopharmaceutical company, reported the publication of preclinical data highlighting the potential of soquelitinib, the Company’s lead ITK inhibitor program, as a novel approach to modulate tumor immunity (Press release, Corvus Pharmaceuticals, DEC 4, 2024, View Source [SID1234648787]). The data was published in npj Drug Discovery (part of the Nature portfolio of journals), an open access, international, peer-reviewed journal dedicated to publishing the highest quality research relevant to all aspects of drug design and discovery.

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The publication, entitled "Synthesis and characterization of soquelitinib a selective ITK inhibitor that modulates tumor immunity," includes a detailed overview of soquelitinib’s mechanism of action – suppressing Th2 and Th17 cytokine production and sparing Th1 cytokines – that serves as a novel approach to cancer immunotherapy, both as a single agent and in combination with immune checkpoint inhibitors. The data also shows that soquelitinib increases effector function of cytotoxic CD8 positive T cells and leads to an increase in memory T cells with enhanced effector function.

"We continue to build awareness of the unique potential of soquelitinib and ITK inhibition as a novel therapy that modulates parallel signaling pathways in the immune system for the treatment of oncology and immune diseases," said Richard A. Miller, M.D., co-founder, president and chief executive officer of Corvus. "This publication in npj Drug Discovery highlights foundational work characterizing key properties and mechanisms of soquelitinib conducted at Corvus and with academic collaborators, and we are excited to now be in clinical development for PTCL and atopic dermatitis, along with a broad range of additional opportunities for soquelitinib and our next-generation ITK inhibitors."

The published research was a result of collaborations between scientists at Corvus and researchers at the University of Michigan, The Ohio State University, Peking University, Stanford University and Angel Pharmaceuticals Co., Ltd. The publication is available online at the Nature website and on the Publications and Presentations page of the Corvus website.

Corvus is currently developing soquelitinib and its next-generation ITK inhibitors for oncology and immune diseases. The Company is enrolling patients in a registrational Phase 3 clinical trial in patients with relapsed peripheral T cell lymphoma (PTCL) and a randomized, placebo-controlled Phase 1 clinical trial in patients with moderate to severe atopic dermatitis. The Company plans to initiate a Phase 1 clinical trial of soquelitinib in patients with solid tumors.

On December 4, 2024 Can-Fite BioPharma Ltd. (NYSE American: CANF) (TASE: CANF), a biotechnology company advancing a pipeline of proprietary small molecule drugs that address oncological and inflammatory diseases, reported that a patient currently treated with Namodenoson in a compassionate use program in Can-Fite’s Phase II Liver Cancer Study has an overall survival time of 8 years with a complete response (Press release, Can-Fite BioPharma, DEC 4, 2024, View Source [SID1234648786]).

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The patient, who suffered from advanced liver cancer was enrolled in the former Can-Fite Phase II study, continue to be treated with Namodenoson, and has now an overall survival of 8 years, with disappearance of ascites, normal liver function, good quality of life and is defined as a long term complete response.

Can-Fite is currently enrolling patients in Israel, Europe and the US for a pivotal Phase III clinical study for patients with advanced HCC as a 2nd or 3rd line treatment and Namodenoson is administered twice daily orally. The study protocol has been agreed upon with U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA).

Namodenoson has Orphan Drug status with both the FDA and EMA, as well as Fast Track Status with the FDA for the treatment of HCC. A compassionate use program has been ongoing in Israel and Romania.

"With a very favorable safety profile and anti-cancer effect of Namodenoson, we are now enrolling patients for the pivotal Phase III clinical study where we expect to prolong patients’ overall survival, and see a response similar to that of the patient who has now been treated with Namodenoson for 8 years. The uniqueness of Namodenoson which specifically acts against the tumor cells and protects the normal liver cells, is the rationale for the conductance of the current trial," stated Prof. Salomon Stemmer, a leading key opinion leader, at the Institute of Oncology, Rabin Medical Center, Israel.

According to the American Cancer Society, liver cancer accounts for more than 700,000 deaths globally each year. HCC is commonly aggressive with poor survival rates. As new drugs that effectively and safely treat HCC are developed and approved, the market for HCC treatments is estimated by Delveinsight to reach $6.1 billion by 2027 for the G8 countries.

About Namodenoson

Namodenoson is a small orally bioavailable drug that binds with high affinity and selectivity to the A3 adenosine receptor (A3AR). Namodenoson was evaluated in Phase II trials for two indications, as a second line treatment for hepatocellular carcinoma, and as a treatment for non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). A3AR is highly expressed in diseased cells whereas low expression is found in normal cells. This differential effect accounts for the excellent safety profile of the drug.