On October 16, 2023 Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics" hereafter) reported that the clinical results of first-in-human study of FGFR4 inhibitor Irpagratinib（ABSK011）and the clinical results of first-in-human dose-escalating of PD-L1 inhibitor ABSK043 with advanced solid tumors will be presented at the 2023 European Society for Medical Oncology（ESMO）annual meeting to be held in Spain, from October 20 to 24, 2023 (Press release, Abbisko Therapeutics, OCT 16, 2023, View Source [SID1234636035]). The Irpagratinib BID cohorts demonstrated a promising antitumor activity with an ORR of 40.7% in FGF19+ HCC pts with prior therapies.Both research results will be the first of such release by a Chinese company for the respective target.

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Abbisko will present the following posters at the ESMO (Free ESMO Whitepaper) conference:

Title:

First-in-human study of ABSK-011, a novel, highly selective fibroblast growth factor receptor (FGFR) 4 inhibitor for treating advanced hepatocellular carcinoma (HCC) with FGF19 overexpression

Background:

FGF19 overexpression (+) is in ~ 30% of HCC with poor prognosis1.
FGF19/FGFR4 signaling axis could be a therapeutic target for HCC2 (Figure 1).
ABSK-011 is an oral, highly selective, and potent FGFR4 inhibitor for treating FGF19+ HCC.
Conclusion:

ABSK-011 was well-tolerated in HCC pts.
BID cohorts demonstrated a promising antitumor activity with an ORR of 40.7% in FGF19+ HCC pts with prior therapies, which suggests that ABSK-011 may have clinical benefit through biomarker selection of FGF19.
The study is still ongoing, and the efficacy of BID cohorts warrants further investigation.
Title:

First-in-human dose-escalating study of ABSK043, a novel and oral small-molecule inhibitor of PD-L1, in patients with advanced solid tumors
Background:

Immunotherapies targeting the PD-1/PD-L1 pathway with therapeutic antibodies have shown remarkable anti-tumor effects.
ABSK043 is an oral small molecule PD-L1 inhibitor that potently blocks PD-1/PD-L1 interaction. Comparing to antibodies, small molecules render lower immunogenic risk and convenience in administration.
Here, we report the preliminary results from the dose escalation part of first-in-human (FIH) study of ABSK043 in patients with advanced solid tumors (NCT04964375).
Conclusion:

ABSK043 was well tolerated up to 1000 mg BID with no DLT reported and has a safety profile consistent with monoclonal antibody immune checkpoint inhibitors.
On-target PD effects were consistent with PD-L1 inhibition and data reported by anti-PD-(L)1 mAbs.
Preliminary anti-tumor activity was observed, and further investigation is warranted to explore the efficacy in a larger number of patients.

On October 16, 2023 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL kinase inhibitors for severe unmet medical needs, reported that a poster and an oral presentation summarizing completed studies with its lead product candidate bemcentinib will be presented at the upcoming European Society of Clinical Oncologists (ESMO) (Free ESMO Whitepaper) Annual Meeting 2023, to be held October 20-24 in Madrid (Press release, BerGenBio, OCT 16, 2023, View Source [SID1234636034]).

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Enriqueta Felip, M.D., Ph.D., Head of the Thoracic Cancer Unit at Vall d’Hebron University Hospital, Spain will present the following poster summarizing the final results from the BGBC008 Phase II study of bemcentinib in combination with pembrolizumab in 2L NSCLC:

Poster Title: Final top-line results of the BGBC008 phase 2, multicenter study of bemcentinib and pembrolizumab (bem+pembro) in 2nd line (2L) advanced non-squamous (NS) non-small cell lung cancer (NSCLC) (NCT03184571) of S
Session Date: Onsite poster display date, Monday October 23
Poster Board Number: 1440P

The poster will be available on BerGenBio’s website shortly following presentation.

In addition, Dr. Oddbjorn Straume, M.D., Ph.D., Assistant Professor, Clinical Science at the Haukeland University Hospital in Bergen, Norway will make an oral presentation summarizing the results of the Investigator Led Study LBA52 with bemcentinib in addition to pembrolizumab or dabrafenib/trametinib in 1L and 2L metastatic melanoma patients:

Oral Presentation Title: A randomized Phase Ib/II study of the selective small molecule AXL inhibitor bemcentinib in combination with either dabrafenib/trametinib or pembrolizumab in patients with metastatic melanoma

Session Name: LBA 52 "Melanoma and other skin tumors"
Session Date and Time: Saturday October 21, 15:50-15:55 CET
Location: Leon Auditorium, Hall 7

Martin Olin, Chief Executive Officer of BerGenBio, commented: "We are pleased to share more data on bemcentinib which we believe substantiates our strategy to focus on the treatment of Non-Small Cell Lung Cancer patients with a goal of potentiating the effects of standard of care treatments. We thank the patients who participated in these studies, their families, and all participating investigators as well as their clinical and nursing staff for contributing to our understanding of bemcentinib as a potential cancer therapeutic."

On October 16, 2023 Phanes Therapeutics, Inc. (Phanes), a clinical stage biotech company focused on innovative drug discovery and development in oncology, reported that it has entered into a clinical collaboration agreement with Merck (known as MSD outside the US and Canada) to study PT886, its first-in-class bispecific antibody targeting claudin 18.2 and CD47, in combination with Merck’s anti-PD-1 therapy, KEYTRUDA (pembrolizumab), in patients with claudin 18.2 positive gastric or gastroesophageal junction (GEJ) adenocarcinomas (Press release, Phanes Therapeutics, OCT 16, 2023, View Source [SID1234636033]). PT886 was assembled using Phanes’ proprietary bispecific antibody platforms PACbody and SPECpair and was granted orphan drug designation (ODD) for the treatment of pancreatic cancer by the FDA last year.

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Phanes is currently enrolling patients in a multi-center Phase I clinical trial of PT886 in the U.S. evaluating the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary efficacy in patients with locally advanced or metastatic gastric, GEJ, or pancreatic cancer that have progressed after all available standard therapy or for which standard therapy has proven to be ineffective, intolerable, or is considered inappropriate (NCT05482893). The next phase of Phanes’ study is investigating the therapeutic potential of PT886 as a combination therapy in gastric, GEJ and pancreatic cancers. The clinical collaboration with Merck will evaluate PT886 in combination with KEYTRUDA (pembrolizumab) in patients with claudin 18.2 positive gastric or GEJ adenocarcinomas with or without chemotherapy.

"Phanes is very excited about partnering with Merck on this novel approach to treat patients with gastric or gastroesophageal cancers," said Dr. Ming Wang, Founder and CEO of Phanes. "Claudin 18.2 is a clinically validated target and is over-expressed in these types of GI tumors. We believe the mechanisms of PT886 and pembrolizumab are complementary and the combination has the potential to improve outcomes for patients. This collaboration marks another milestone for Phanes in fulfilling our vision of developing innovative approaches to treat cancer."

KEYTRUDA is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

ABOUT PT886

PT886 is a first-in-class bispecific antibody targeting claudin 18.2 and CD47. It was constructed using Phanes’ proprietary bispecific antibody platforms PACbody and SPECpair and was granted orphan drug designation (ODD) for the treatment of pancreatic cancer. PT886 is expected to directly kill tumor cells via both the ADCP activity of macrophages and ADCC activity of NK cells, and by targeting both claudin 18.2 and CD47 expressed on the surface of tumor cells, it can broaden the tumor killing spectrum. Additionally, PT886 is expected to induce the presentation of tumor neoantigens by channeling tumor cells into phagocytotic antigen presenting cells (APCs) and stimulate the adaptive immune system by indirectly activating T cell killing of claudin 18.2 expressing tumor cells through recognition of tumor neoantigens. The anti-CD47 arm of PT886 is differentiated and has demonstrated minimum binding to human red blood cells while maintaining strong binding activity to CD47 on tumor cells, thus improving the benefit/risk profile versus other CD47 molecules.

On October 16, 2023 Abbisko Therapeutics Co., Ltd. ("Abbisko" hereafter) reported that the results of the company’s two preclinical studies published at the 35th International Molecular Targets and Cancer Treatment Conference (EORTC) be held in Boston, U.S. (Press release, Abbisko Therapeutics, OCT 16, 2023, https://www.prnewswire.com/news-releases/abbisko-presented-two-preclinical-research-results-at-the-35th-international-molecular-targets-and-cancer-treatment-conference-eortc-nci-aacr-301957292.html [SID1234636032]). These two research results respectively demonstrate the latest preclinical research progress of the next generation of PRMT5*MTA inhibitors and small molecule brain penetrant PD-L1 inhibitors in Abbisko’s pipeline. As the world’s highest-quality research conference focusing on molecular targeting and tumor treatment, the ENA conference collects the most cutting-edge researches on innovative drugs and therapies in the field of tumor treatment.

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Abbisko presented the following posters at the ENA conference:

Title: Discovery and characterization of an MTA-cooperative and brain-penetrant PRMT5 inhibitor

Poster number: C130

Session date and time: Saturday, October 14 | 12:30 pm-4:00 pm

Session location: Level 2, Exhibit Hall D

Background: MTAP is homozygous deleted in ~50% in glioblastoma and many other cancers. PRMT5*MTA inhibition has been shown to be synthetic lethal with MTAP deletion. First generation PRMT5 inhibitors could not distinguish between PRMT5*MTA or PRMT5 alone, thus limited by their shallow therapeutic windows in clinical use. Development of selective PRMT5*MTA inhibitors may improve not only safety but also therapeutic efficacy. Leveraging advanced computation-aided structural analysis and medicinal chemistry design, we have discovered a potent and selective MTA-cooperative and brain-penetrable PRMT5 inhibitor ABK-PRMT5-1, which demonstrates strong anti-tumor activity and brain-penetrating activity in various preclinical models.

Conclusion：

ABSK-PRMT5-1 strongly inhibits cell proliferation in MTAP-deleted cancer cell lines, with minimal effects on MTAP wildtype cell lines. Furthermore, it significantly reduces SDMA in MTAP-deleted cancer cell lines. Oral administration of ABSK-PRMT5-1 strongly inhibits tumor growth in MTAP-deleted xenograft tumor models. In addition, ABSK-PRMT5-1 demonstrates strong brain penetration with excellent Kp values in animals. DMPK and safety profiling shows good overall drug-like properties of ABK-PRMT5-1. ABK-PRMT5-1, presented here by Abbisko Therapeutics, is a highly selective MTA-cooperative and brain-penetrable PRMT5 inhibitor. Its superior profile supports fast-track preclinical development.

Title: Discovery and characterization of a novel small molecule brain penetrant PD-L1 inhibitor

Poster number : B151

Session date and time: Friday, October 13 | 12:30 pm-4:00 pm

Session location: Level 2, Exhibit Hall D

Background: Immunotherapy has revolutionized cancer treatment in the last decade. Several monoclonal PD-1 and PD-L1 antibodies have been approved for treating various cancers. Small molecule PD-L1 inhibitors with brain-penetrating ability may have potential to overcome the limitations of antibodies and bring benefit for patients with intracranial tumors. Leveraging advanced computation-aided structural analysis and medicinal chemistry design, we have successfully discovered an innovative orally available small molecule PD-L1 inhibitor ABSK044. In preclinical experiments, this compound demonstrates robust T-cell activating ability, strong anti-tumor efficacy, and brain-penetrating activity.

Conclusion：

ABSK044 strongly inhibits PD-1-PD-L1 interaction with an IC50 less than 1nM in vitro and very potently rescues PD-L1-induced suppression of T cell activation signaling in cells. Furthermore, it efficiently rescues cytokine production in CD8+ T cells suppressed by PD-L1, reaching a level comparable to that of PD-L1 antibodies. In in vivo studies, oral administration of ABSK044 strongly inhibits tumor growth to an extent similar to therapeutic anti-PD-L1 antibodies. Notably, ABSK044 demonstrates excellent brain penetration with a Kp value exceeding 0.4. DMPK and safety profiling demonstrate excellent drug-like properties of ABSK044.

ABSK044, presented here by Abbisko Therapeutics, is a highly potent and orally available small molecule PD-L1 antagonist with brain-penetrating activity. Its superior profile supports its fast-track preclinical development.

On October 16, 2023 Nuvalent, Inc. (Nasdaq: NUVL), a clinical-stage biopharmaceutical company focused on creating precisely targeted therapies for clinically proven kinase targets in cancer, reported the pricing of its previously announced underwritten public offering of 5,357,143 shares of Class A common stock at a price to the public of $56.00 per share (Press release, Nuvalent, OCT 16, 2023, View Source [SID1234636031]). All shares are being offered by Nuvalent. The gross proceeds to Nuvalent from the offering, before deducting underwriting discounts, commissions and other offering expenses, are expected to be approximately $300.0 million. The offering is expected to close on October 19, 2023, subject to the satisfaction of customary closing conditions. In addition, the underwriters have a 30-day option to purchase up to an additional 803,571 shares of Class A common stock at the public offering price less underwriting discounts and commissions.

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J.P. Morgan, TD Cowen, Piper Sandler and BMO Capital Markets are acting as joint book-running managers for the offering. Wedbush Securities is acting as a manager.

The shares are being offered by Nuvalent pursuant to an automatically effective shelf registration statement that was filed with the Securities and Exchange Commission ("SEC") on March 16, 2023. The offering is being made only by means of a prospectus and prospectus supplement that form a part of the registration statement. A preliminary prospectus supplement relating to and describing the terms of the offering has been filed with the SEC and may be obtained for free by visiting the SEC’s website at www.sec.gov. A final prospectus supplement relating to the offering will be filed with the SEC. Copies of the final prospectus supplement and the accompanying prospectus can be obtained, when available, from: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, by telephone at (866) 803-9204 or by email at [email protected]; Cowen and Company, LLC, 599 Lexington Avenue, New York, NY 10022, by telephone at (833) 297-2926 or by email at [email protected]; Piper Sandler & Co., 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, Attention: Prospectus Department, by telephone at (800) 747-3924, or by email at [email protected]; and BMO Capital Markets Corp., Attn: Equity Syndicate Department, 151 W 42nd Street, 32nd Floor, New York, NY 10036, by telephone at (800) 414-3627 or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or 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 jurisdiction.