On September 18, 2024 Abbisko Therapeutics (HKEX: 02256) reported the receipt of the ESMO (Free ESMO Whitepaper) 2024 Best Poster Award on September 16, 2024. The award was received for the presentation titled "Updated Safety and Efficacy of Irpagratinib (ABSK011) in advanced hepatocellular carcinoma (aHCC) with FGF19 overexpression from a Phase 1 study" (Press release, Abbisko Therapeutics, SEP 18, 2024, View Source;2024-abbisko-announces-updated-clinical-data-of-irpagratinib-in-hcc-302251728.html [SID1234646724]). The update data from ABSK-011-101 study showed a tolerable safety profile and promising anti-tumor activity of Irpagratinib monotherapy in aHCC. Of note, in aHCC patients who were pretreated with both immune checkpoint inhibitor (ICI) and Tyrosine Kinase Inhibitor (TKI)—a population with high unmet need in the current treatment paradigm—the observed ORR and DCR was 44.8% and 79.3%, respectively, with a median duration of response (mDoR) of 7.4 months and median progression free survival (mPFS) of 5.5 months.

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The poster, #983P, was presented at the Hepatocellular Carcinoma poster session on Sunday, September 16, 2024. The Best Poster Award was given at the conclusion of the Sunday Poster Session, with only one recipient being honored in HCC poster session.

As of September 5, 2024, 122 patients have been enrolled, including 74 in the BID cohort with doses consisting of 160mg BID, 220mg BID, and 300mg BID. 5.4% of patients were BCLC Stage B, and 89.2% BCLC Stage C, 64.9% had a Child-Pugh (CP) Score of 5, 27% CP Score of 6, and 6.8% CP Score of 7. 64.9% of patients received multiple lines of prior therapy, 85.1% of patients had previously been treated with ICIs, and 75.7% of patients had previously been treated with both ICIs and mTKIs.

The efficacy data show that forty pre-treated HCC patients with FGF19 overexpression were treated with irpagratinib 220 mg BID. Among the 38 evaluable patients, the response rate was 36.8% (14/38), and the disease control rate (DCR) was 78.9% (30/38). The response rate from the subset of patients who had previously received ICI and mTKI therapy was 44.8% (13/29). The longest observed DoR was 16.4 months and the mDoR was 7.4 months. DCR was 79.3% (23/29). mPFS was 5.5 months.

Safety data show one dose-limiting toxicity (DLT) was observed in the 300 mg BID cohort. The most common treatment-related adverse effects (TRAEs, >20%) were ALT elevation, diarrhea, AST elevation, hyperphosphatemia, bilirubin elevation, alkaline phosphatase elevation, platelet decrease, and total bile acid elevation. Grade 3-4 treatment-related adverse events (>5%) included AST elevation, ALT elevation, and diarrhea. No grade 5 adverse events occurred.

HCC is the main type of liver cancer, accounting for 85% to 90% of primary liver cancers. HCC is highly malignant, about 30% of which have abnormally high FGFR4 expression and a poor prognosis, and the existing treatment methods still cannot meet the long-term survival benefits. Currently, there is no approved standard of care for HCC patients who have progressed from first-line ICI-based therapies. The FGF19/FGFR4 signaling axis could be a novel therapeutic target for HCC. ABSK-011, a potent FGFR4 inhibitor, demonstrated a tolerable safety profile and promising anti-tumor activity as a single agent. Notably, the irpagratinib 220mg BID regimen exhibited a 44.8% ORR, 7.4 months mDoR and 5.5 months mPFS in heavily pre-treated HCC patients who had received both ICI and mTKI therapy, supporting further late-stage development of irpagratinib in such populations with substantial unmet medical need.

In addition, the design of the phase II study of pimicotinib in combination with chemotherapy and with/without toripalimab as first-line treatment for advanced pancreatic ductal adenocarcinoma (PDAC) has been presented.

About Irpagratinib (ABSK011)

Irpagratinib is a highly selective FGFR4 small molecule inhibitor intended for the treatment of advanced solid tumors that present with abnormalities in the FGF19/FGFR4 signaling pathway (e.g., ligand FGF19 amplification/overexpression, FGFR4 mutation/amplification/fusion), including advanced HCC, cholangiocarcinoma, breast cancer, among others. The FGFR4 signaling pathway is a recognized and promising target for treating HCC. Clinical data with irpagratinib have demonstrated improved potency and anti-tumor efficacy, among other favorable therapeutic properties, compared to competitors.

On September 18, 2024 Aptevo Therapeutics Inc. (Nasdaq:APVO), a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported the closing of its previously announced offering of (i) 9,090,910 shares of its common stock or pre-funded warrants in lieu thereof and (ii) warrants to purchase up to an aggregate of 18,181,820 shares of its common stock (the "Common Warrants") at a purchase price of $0.33 per share and associated Common Warrant in a registered direct offering priced at-the-market under Nasdaq rules (Press release, Aptevo Therapeutics, SEP 18, 2024, View Source [SID1234646723]). Each share of common stock is being offered together with two Common Warrants, each to purchase one share of common stock. The Common Warrants have an exercise price of $0.33 per share, are exercisable upon stockholder approval, and will expire five years following the date stockholder approval.

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Roth Capital Partners acted as placement agent of the offering. Gross proceeds, before deducting placement agent fees and commissions and offering expenses, were to be approximately $3.0 million. The company intends to use the net proceeds from the offering for the continued clinical development of its product candidates, working capital, and other general corporate purposes.

The securities described above were offered pursuant to a registration statement on Form S-1 (File No. 333-281892), that was declared effective by the U.S. Securities and Exchange Commission ("SEC"), on September 16, 2024. The offering was made solely by means of a prospectus. Copies of the accompanying prospectus relating to and describing the terms of the offering may be obtained at the SEC’s website at www.sec.gov or by contacting Roth Capital Partners, LLC, 888 San Clemente Drive, Suite 400, Newport Beach, CA 92660 or by email at [email protected]. This press release does not and shall not constitute an offer to sell or the solicitation of an offer to buy any 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 registration or qualification under the securities laws of any such state or other jurisdiction. All offers were made only by means of a prospectus, including a prospectus supplement, forming a part of the effective registration statement.

The Company also amended certain existing warrants that were previously issued in July 2024, April 2024 and November 2023 to purchase up to 11,822,774 shares of the Company’s common stock and have exercise price of $0.515 per share, effective upon the closing of the offering, such existing warrants have a reduced exercise price of $0.33 per share and shall become exercisable upon stockholder approval.

On September 19, 2024 Ultragenyx Pharmaceutical Inc. (NASDAQ: RARE), a biopharmaceutical company focused on the development and commercialization of novel therapies for rare and ultrarare diseases, reported the grant of 62,555 restricted stock units of the company’s common stock to 16 newly hired non-executive officers of the company (Press release, Ultragenyx Pharmaceutical, SEP 18, 2024, View Source [SID1234646722]). The awards were approved by the compensation committee of the company’s board of directors and granted under the Ultragenyx Employment Inducement Plan, with a grant date of September 16, 2024, as an inducement material to the new employees entering into employment with Ultragenyx in accordance with Nasdaq Listing Rule 5635(c)(4).

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The restricted stock units vest over four years, with 25% of the underlying shares vesting on each anniversary of the grant date, subject to the employee being continuously employed by the company as of such vesting dates.

On September 18, 2024 Sonnet BioTherapeutics Holdings, Inc. (the "Company" or "Sonnet") (NASDAQ: SONN), a clinical-stage company developing targeted immunotherapeutic drugs, reported the completion of enrollment and initiation of dosing in its Phase 1 SB101 clinical trial of SON-1010 (IL12-FHAB) in adult patients with advanced solid tumors (Press release, Sonnet BioTherapeutics, SEP 18, 2024, View Source [SID1234646721]). The Company expects to report topline data from this study in Q4 2024.

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Pankaj Mohan, Founder and Chief Executive Officer of Sonnet commented, "This milestone is an important step forward in our development program for SON-1010 as a monotherapy. We are encouraged by the data seen to date demonstrating safety and tolerability being well within expected levels. We are hopeful that we will continue to see extended PK/PD, tumor targeting and clinical activity during treatment. We remain committed to bringing this trial to completion and we expect to report topline safety data in Q4 2024."

SB101 is the Company’s open-label, adaptive-design dose-escalation study to assess the safety, tolerability, and PK/PD of SON-1010 administered to patients with advanced solid tumors. The study enrolled 24 subjects. Primary outcome measures for the study are to evaluate the safety and tolerability of SON-1010 and establish the maximum tolerated dose (MTD) of SON-1010.

SON-1010 is the Company’s proprietary version of recombinant human interleukin-12 (rhIL-12), configured using Sonnet’s Fully Human Albumin Binding (FHAB) platform, which extends the half-life and activity of the IL-12 component due to binding native albumin in the serum and targets the tumor microenvironment (TME) by strongly binding gp60 and Secreted Protein Acidic and Rich in Cysteine (SPARC).

As previously announced, the safety of SON-1010 was reviewed by the Safety Review Committee at each step during dose escalation. The trial uses a ‘desensitizing’ first dose to take advantage of the known tachyphylaxis with rhIL-12, which minimizes toxicity and allows higher maintenance doses. No dose-limiting toxicities have occurred to date. The safety and toxicity profile that has developed is typical for a Phase 1 oncology trial, with the majority of adverse events (AEs) being reported as mild. All have been transient, with no evidence of cytokine release syndrome.

As previously announced, one patient with progressive endometrial sarcoma receiving SON-1010 monotherapy in SB101 had stable disease (SD) for almost 2 years before progressing – her ascites had resolved and tumors had shrunk at one point but she never reached a partial response (PR) by Response Evaluation Criteria in Solid Tumors (RECIST) rules. Cytokine analysis following each dose in that study revealed controlled and prolonged induction of interferon gamma (IFNγ) that peaked at 24 to 48 hours and returned to baseline within 2 to 4 weeks. A small increase in IL-10 was observed with each dose as expected in response to IFNγ. There was either a minimal or no signal for IL-1β, IL-6, IL-8, and TNFα, and there was no indication of any potential for cytokine release syndrome (CRS) at these doses.

For more information about the SB101 Phase 1 trial in adult patients with advanced solid tumors visit www.clinicaltrials.com and reference identifier NCT05352750.

About SON-1010

SON-1010 is a candidate immunotherapeutic recombinant drug that links unmodified single-chain human IL-12 with the albumin-binding domain of the single-chain antibody fragment A10m3. This was selected to bind albumin both at normal pH, as well as at the acidic pH typically found in the TME. The FHAB technology targets tumor and lymphatic tissue, providing a mechanism for dose sparing and an opportunity to improve the safety and efficacy profile of not only IL-12, but a variety of potent immunomodulators that can be linked using the platform. Interleukin-12 can orchestrate a robust immune response to many cancers and pathogens. Given the types of proteins induced in the TME, such as the Secreted Protein and Rich in Cysteine (SPARC) and glycoprotein 60 (GP60), several types of cancer such as non-small cell lung cancer, melanoma, head and neck cancer, sarcoma, and some gynecological cancers are particularly relevant for this approach. SON-1010 is designed to deliver IL-12 to local tumor tissue, turning ‘cold’ tumors ‘hot’ by stimulating IFNγ, which activates innate and adaptive immune cell responses and increases the production of Programed Death Ligand 1 (PD-L1) on tumor cells.

About the SB101 Phase 1 Trial

This first-in-human study is primarily designed to evaluate the safety of multiple ascending doses of SON-1010 in cancer patients and is being conducted at several sites across the United States. While the optimal dose is unknown at this stage, the potential to target tumors, the extended PK mechanism, and our preclinical data suggest the therapeutic dose may be lower compared to native human IL-12. The study, utilizing a standard 3+3 oncology design in at least five cohorts, should establish the MTD using subcutaneous injections of SON-1010 every 3 to 4 weeks. The primary endpoint explores the safety and tolerability of SON-1010, with key secondary endpoints intended to measure pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, and anti-tumor activity. This study will form the basis for potential combinations with other types of immunotherapies and the future development of bispecific candidates using the FHAB platform.

On September 18, 2024 Purple Biotech Ltd. ("Purple Biotech" or "the Company") (NASDAQ/TASE: PPBT), a clinical-stage company developing first-in-class therapies that overcome tumor immune evasion and drug resistance, reported new positive biomarker findings for its lead oncology therapeutic candidate CM24 (Press release, Purple Biotech, SEP 18, 2024, View Source [SID1234646720]). These data were presented yesterday at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Special Conference on Advances in Pancreatic Cancer Research currently ongoing in Boston, in a poster titled, "Exploratory biomarker evaluation of the randomized Phase 2 cohort of CM24 in combination with nivolumab and chemotherapy in advanced/metastatic pancreatic cancer".

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"We are excited to present additional positive data from our Phase 2 study with CM24. CEACAM1 as a novel target in oncology continues to be supported by these data, underscoring its potential given its high expression on cancer cells, tumor infiltrating leucocytes and on NETs, suggesting the potential multiple roles of CM24 in overcoming immune evasion," stated Purple Biotech CEO Gil Efron. "Moreover, these data enable us to potentially design biomarker- guided studies for CM24 for the treatment of pancreatic ductal adenocarcinoma (PDAC), as well as other cancers."

Purple Biotech’s Phase 2 study is evaluating CM24 in combination with Bristol Myers Squibb’s PD-1 inhibitor nivolumab plus standard of care (SoC) chemotherapy as a second line treatment of patients with PDAC and compared to SoC chemotherapy alone. Sixty-three patients have been enrolled in the randomized study across 18 centers in the U.S., Spain, and Israel.

The following is a summary of findings presented in the poster:

Mechanism of Action

CM24 blocks CEACAM1 interactions, which have key roles in cancer progression, immune escape and metastasis. CEACAM1 is part of the NET complex, involved in tumor immune evasion, metastasis and cancer-associated thrombosis, affecting patient survival. Purple Biotech has previously presented data that demonstrates that CM24 binds to CEACAM1 on NETs, suppresses NET-induced migration of cancer cells and inhibits in-vivo tumor metastasis. In the poster, Purple Biotech presents data that demonstrates that CM24 also inhibits NET-induced platelet aggregation, an in-vitro assay imitating the thrombosis process.

CM24+nivolumab+Nal-IRI/5FU/LV treatment of PDAC patients reduced serum levels of the NET marker, MPO, and showed potential overall survival (OS) benefit to patients with reduced post-dose MPO as compared to the control arm.

NET Marker MPO as a Potential Serum Biomarker for Patient Selection for CM24-Based Therapy

An analysis of patients with serum MPO levels < 350 ng/mL, demonstrated a potential 62% reduction in risk of death (HR=0.38) for CM24+nivolumab+Nal-IRI/5FU/LV therapy in PDAC patients, and prolongation of 3.3 months in median OS. This compared to an analysis of all patients which demonstrated a potential 25% reduction in risk of death (HR=0.75) and prolongation of 2.1 months in median OS.

High Tumor CEACAM1 & Low PDL1 as Potential Biomarkers for CM24-Based Therapy

An analysis of patients with high CEACAM1+tumor cells (H-score > 115) or low PDL1 (CPS ≤ 1) demonstrated a potential 45% and 65% reduction in risk of death (HR=0.55 and 0.35), respectively.

Combining these two potential biomarkers, suggests augmented outcome of 90% reduction in risk of death (HR=0.1) for CM24+nivolumab+Nal-IRI/5FU/LV therapy in PDAC patients, and prolongation of 4.1 months in median OS (p value 0.01).

"A serum biomarker for patient selection is a major advantage for cancer patients in general and PDAC patients in particular. The additional interim data suggesting serum NET levels as a potential biomarker for improving the outcome of CM24-based therapy, together with the ability of this therapy to reduce serum NET levels in PDAC patients and to inhibit NET-related activities in vitro, add supporting evidence for NETs as a new mechanism of action (MoA) and potential biomarker for CM24-based therapy," said Dr. Hadas Reuveni, VP R&D of Purple Biotech. "Additional encouraging results suggesting that the CM24/ nivolumab/chemotherapy effect is most pronounced among patients with high CEACAM1 expression and low PDL1 also relate to the CM24/nivolumab MoA and support the CM24/nivolumab combined treatment. This may open a new opportunity for patients who are not eligible for anti-PD1 therapy in various indications. A larger sample size is required to confirm the results and better define the cutoff values."

Interim data from Purple Biotech’s Phase 2 study presented in June at the 2024 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting demonstrated improvement in OS, progression free survival (PFS), objective response rate (ORR) and all other efficacy endpoints in the CM24+nivolumab+Nal-IRI/5FU/LV experimental arm as compared with the SoC control arm. Topline data are expected in the fourth quarter of 2024.

The poster is available on the Publications section of Purple Biotech’s website and in the following link: View Source