On April 23, 2025 Summit Therapeutics Inc. (NASDAQ: SMMT) ("Summit," "we," or the "Company") today noted that Akeso, Inc. (Akeso, HKEX Code: 9926.HK) reported that the Phase III clinical trial, HARMONi-6 or AK112-306, met its primary endpoint of progression-free survival (PFS) (Press release, Summit Therapeutics, APR 23, 2025, View Source [SID1234652085]). HARMONi-6 is evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, a PD-1 inhibitor, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC) irrespective of PD-L1 expression. HARMONi-6 is a single region, multi-center, Phase III study conducted in China sponsored by Akeso with all relevant data exclusively generated, managed, and analyzed by Akeso.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

At a prespecified interim analysis conducted by an Independent Data Monitoring Committee, ivonescimab plus chemotherapy demonstrated a statistically significant and clinically meaningful improvement in PFS by blinded independent central radiology review committee (BICR) compared to tislelizumab plus chemotherapy. The PFS benefit was demonstrated in patients with either PD-L1-positive or PD-L1-negative tumors. Akeso noted that no new safety signals were identified in this Phase III study. The full data set for HARMONi-6 is planned to be presented at an upcoming major medical conference later this year.

Prior to HARMONi-6, there were no known Phase III clinical trials in NSCLC which have shown a statistically significant improvement compared to PD-(L)1 inhibitor therapy in combination with chemotherapy in a head-to-head setting. Following the success of Akeso’s HARMONi-2 study in China where the PFS benefit was observed in a monotherapy setting for patients whose squamous or non-squamous tumors were positive for PD-L1 expression, this is the second time in which ivonescimab-based regimens have become the first known investigational therapy to demonstrate a statistically significant benefit compared to standard-of-care PD-(L)1 inhibitor-based regimens.

"Ivonescimab has the opportunity to make a significant, positive difference, potentially providing patients with the next generation of treatment options against insidious solid tumors beginning with non-small cell lung cancer," stated Dr. Maky Zanganeh, President and Co-Chief Executive Officer of Summit.

Summit is currently enrolling patients in the HARMONi-3 study. HARMONi-3 is a multiregional Phase III clinical trial sponsored by Summit which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab, an anti-PD-1 antibody, combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC. HARMONi-3 is currently enrolling patients globally and is conducted with registrational intent for the United States and other regions within Summit’s license territories.

"Our aligned mission with Akeso seeks to bring ivonescimab to as many patients around the world who can potentially benefit as quickly as possible," added Robert W. Duggan, Chairman and Co-Chief Executive Officer of Summit. "We are incredibly proud of Akeso’s accomplishment with the HARMONi-6 trial."

About Ivonescimab

Ivonescimab, known as SMT112 in Summit’s license territories, North America, South America, Europe, the Middle East, Africa, and Japan, and as AK112 in China and Australia, is a novel, potential first-in-class investigational bispecific antibody combining the effects of immunotherapy via a blockade of PD-1 with the anti-angiogenesis effects associated with blocking VEGF into a single molecule. Ivonescimab displays unique cooperative binding to each of its intended targets with multifold higher affinity to PD-1 when in the presence of VEGF.

This could differentiate ivonescimab as there is potentially higher expression (presence) of both PD-1 and VEGF in tumor tissue and the tumor microenvironment (TME) as compared to normal tissue in the body. Ivonescimab’s tetravalent structure (four binding sites) enables higher avidity (accumulated strength of multiple binding interactions) in the TME (Zhong, et al, SITC (Free SITC Whitepaper), 2023). This tetravalent structure, the intentional novel design of the molecule, and bringing these two targets into a single bispecific antibody with cooperative binding qualities have the potential to direct ivonescimab to the tumor tissue versus healthy tissue. The intent of this design, together with a half-life of 6 to 7 days after the first dose (Zhong, et al, SITC (Free SITC Whitepaper), 2023), is to improve upon previously established efficacy thresholds, in addition to side effects and safety profiles associated with these targets.

Ivonescimab was engineered by Akeso Inc. (HKEX Code: 9926.HK) and is currently engaged in multiple Phase III clinical trials. Over 2,300 patients have been treated with ivonescimab in clinical studies globally.

Summit has begun its clinical development of ivonescimab in non-small cell lung cancer (NSCLC), commencing enrollment in 2023 in two multi-regional Phase III clinical trials, HARMONi and HARMONi-3, and the Company has begun to activate clinical trial sites in the United States for HARMONi-7.

HARMONi is a Phase III clinical trial which intends to evaluate ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with a 3rd generation EGFR TKI (e.g., osimertinib). Enrollment in HARMONi was completed in the second half of 2024, and top-line results are expected to be announced in the middle of this year.

HARMONi-3 is a Phase III clinical trial which is intended to evaluate ivonescimab combined with chemotherapy compared to pembrolizumab combined with chemotherapy in patients with first-line metastatic, squamous and non-squamous NSCLC.

HARMONi-7 is a Phase III clinical trial which is intended to evaluate ivonescimab monotherapy compared to pembrolizumab monotherapy in patients with first-line metastatic NSCLC whose tumors have high PD-L1 expression.

In addition, Akeso has recently had positive read-outs in three single-region (China), randomized Phase III clinical trials for ivonescimab in NSCLC: HARMONi-A, HARMONi-2, and HARMONi-6.

HARMONi-A was a Phase III clinical trial which evaluated ivonescimab combined with chemotherapy compared to placebo plus chemotherapy in patients with EGFR-mutated, locally advanced or metastatic non-squamous NSCLC who have progressed after treatment with an EGFR TKI.

HARMONi-2 is a Phase III clinical trial evaluating monotherapy ivonescimab against monotherapy pembrolizumab in patients with locally advanced or metastatic NSCLC whose tumors have positive PD-L1 expression.

HARMONi-6 is a Phase III clinical trial evaluating ivonescimab in combination with platinum-based chemotherapy compared with tislelizumab, an anti-PD-1 antibody, in combination with platinum-based chemotherapy in patients with locally advanced or metastatic squamous non-small cell lung cancer (NSCLC), irrespective of PD-L1 expression.

Ivonescimab is an investigational therapy that is not approved by any regulatory authority in Summit’s license territories, including the United States and Europe. Ivonescimab was approved for marketing authorization in China in May 2024. Ivonescimab was granted Fast Track designation by the US Food & Drug Administration (FDA) for the HARMONi clinical trial setting.

On April 23, 2025 Abdera Therapeutics Inc., a clinical-stage biopharmaceutical company leveraging its advanced antibody engineering ROVEr platform to design and develop tunable precision radiopharmaceuticals for cancer, reported two upcoming presentations at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held from April 25 – 30, 2025 in Chicago, IL (Press release, Abdera Therapeutics, APR 23, 2025, View Source [SID1234652084]). These include: (1) a poster presentation of Abdera’s ongoing Phase 1 clinical trial for ABD-147, a DLL3-targeting radiopharmaceutical, and (2) preclinical data on ABD-320, a 5T4-targeting radiopharmaceutical and Abdera’s second development program.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We are pleased with the progress we’re making at Abdera and are excited to share our developments at AACR (Free AACR Whitepaper) this year," said Lori Lyons-Williams, president and chief executive officer. "Our first-in-human Phase 1 study for ABD-147 is enrolling and dosing patients. We are also unveiling compelling preclinical data for ABD-320, the first radiopharmaceutical therapy in development targeting 5T4. This widely prevalent target is associated with poor outcomes across multiple cancer types and we look forward to advancing ABD-320 into clinical development in the first half of 2026."

Details of the presentations are as follows:

Title: A phase 1a/b, open-label, dose-escalation study of 225Ac-ABD147 for locally advanced or metastatic small cell lung cancer and large cell neuroendocrine carcinoma of the lung following platinum-based chemotherapy
Abstract Number: CT107 / 2
Session: PO.CTP01.01 – Phase I Clinical Trials in Progress 1
Date/Time: April 28, 2025 / 2:00 PM – 5:00 PM
Location: Section 51

Title: 111In/225Ac-ABD320, a novel 5T4-targeted radiopharmaceutical with favorable tumor-to-normal tissue biodistribution and single-dose efficacy in preclinical cancer models
Abstract Number: 580 / 15
Session: PO.ET08.01 – Theranostics and Radiotheranostics
Date/Time: April 27, 2025 / 2:00 PM – 5:00 PM
Location: Section 25

About ABD-147

ABD-147 is a targeted radiopharmaceutical biologic therapy designed to deliver Actinium-225 (225Ac), a highly potent alpha-emitting radioisotope, to solid tumors expressing delta-like ligand 3 (DLL3) with high affinity. DLL3 is a protein in the Notch pathway that is critical for the development and regulation of neuroendocrine versus epithelial cell differentiation in the lungs. In certain high grade neuroendocrine carcinomas including small cell lung cancer (SCLC), DLL3 is upregulated and specifically expressed on the cell surface in more than 80% of cases. In contrast, DLL3 is absent or very rarely expressed on the surface of nonmalignant cells. Given the high specificity of DLL3 expression on cancer cells and the distinct mechanism of action, DLL3 represents a compelling target for treating SCLC and other DLL3+ solid tumors with targeted radiotherapy.

The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to ABD-147 for the treatment of patients with extensive stage small cell lung cancer (ES-SCLC) who have progressed on or after platinum-based chemotherapy and Orphan Drug Designation to ABD-147 for the treatment of neuroendocrine carcinoma. ABD-147 is currently being evaluated in a first-in-human Phase 1 clinical trial in patients with SCLC or large cell neuroendocrine carcinoma of the lung who have previously received platinum-based therapy.

About Small Cell Lung Cancer and Large Cell Neuroendocrine Carcinoma

The global incidence for SCLC and LCNEC has been reported to represent approximately 325,000 patients and is expected to increase 4% annually through 2029. In the U.S., the incidence has been reported to be approximately 35,000 new cases annually. Fifteen percent of all lung cancer cases are high-grade neuroendocrine cancers. These cancers have the most aggressive clinical course of any type of pulmonary tumor and often metastasize to other parts of the body, including the brain, liver and bone. Without treatment, the median survival from diagnosis has been reported to be only two to four months. With treatment, the overall survival at five years is 5% to 10% for SCLC, and 15% to 25% for LCNEC. SCLC and LCNEC generally carry a poor prognosis and new treatment options are urgently needed.

About ABD-320

ABD-320 is a targeted radiopharmaceutical biologic therapy engineered to deliver Actinium-225 (225Ac) to solid tumors expressing 5T4. This oncofetal protein is rarely expressed in normal adult tissues but has been shown to be up-regulated in multiple cancer types, including colorectal, head and neck, non-small cell lung, pancreatic, gastric, mesothelioma, bladder, renal, cervical, ovarian, and breast cancers. By driving tumor cell migration and survival, 5T4 plays a key role in cancer progression and is associated with advanced disease, increased invasiveness, and poor clinical outcomes in solid tumors. ABD-320 was developed leveraging Abdera’s ROVEr platform and is custom-engineered to achieve an ideal balance of tumor uptake and retention while avoiding systemic radiotoxicities. Preclinical data with ABD-320 demonstrates potent anticancer activity. ABD-320 represents the first radiopharmaceutical therapy in development to address 5T4.

On April 23, 2025 Parabilis Medicines (formerly Fog Pharmaceuticals), a clinical-stage biopharmaceutical company committed to creating extraordinary medicines for people living with cancer, reported the presentation of preclinical data on its first-in-class targeted protein degrader of ERG at the upcoming American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting, being held April 25–30, 2025, in Chicago, Illinois (Press release, Parabilis Medicines, APR 23, 2025, View Source [SID1234652083]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

The transcription factor ERG has been a long-recognized high-value target in prostate cancer, where ERG fusions have been implicated in 40-50% of all cases. Despite its relevance, ERG has remained undrugged by conventional inhibitors or first-generation degraders because the protein lacks small molecule binding pockets.

Parabilis’s ERG degrader overcomes this challenge by using the company’s proprietary Helicon peptide technology, which enables intracellular targeting of "flat" protein surfaces. The company’s prostate cancer franchise also includes a selective degrader of androgen receptor (AR) targeting a site outside the canonical androgen-binding site on the protein, thereby addressing a common resistance mechanism that arises in response to AR antagonist therapies. Together Parabilis’s degraders of ERG and AR could potentially provide meaningful and differentiated therapeutic approaches to treat patients with metastatic castrate-resistant prostate cancer (mCRPC).

Full details of the poster are as follows:

Title: "Degradation of the ETS transcription factor ERG by stabilized helical peptide (Helicon) degraders enables pharmacological validation in ERG-fusion prostate cancer models"
Abstract Number: 4246/3
Presentation Date and Time: Tuesday, April 29, 9:00 a.m. – 12:00 p.m. CDT
Session: New and Emerging Cancer Drug Targets
Location: Poster Section 17

On April 23, 2025 Grove Biopharma, a private biotechnology company pioneering its Bionic Biologics platform to develop therapies targeting previously intractable intracellular disease targets, reported the close of a $30 million Series A financing (Press release, Grove Biopharma, APR 23, 2025, View Source [SID1234652082]). The round was led by DCVC Bio with participation from Eli Lilly and Company, InVivium Capital, Walder Ventures, Gradiant Corporation, Mansueto Investments, and others. They join existing seed supporters, including Portal Innovations, where Grove was incubated. Proceeds will be used to further advance Grove Biopharma’s proprietary platform and drive its lead oncology programs towards the clinic.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Bionic Biologics represent a novel therapeutic modality that integrates principles of biologic and synthetic design. This innovative platform enables the targeting of well-validated yet previously intractable disease drivers, unlocking new possibilities for therapeutic intervention. Bionic Biologics combine advancements in precision polymer chemistry with the latest tools of medicinal chemistry, peptide chemistry, AI/ML driven computational chemistry and protein engineering. The result is an integrated platform capable of designing fully synthetic, cell-penetrant, protein-scale molecules that solve protein-scale problems.

"At Grove, we are focused on developing therapeutics for well-understood but historically intractable disease targets, with the goal of delivering better options for patients living with serious illnesses where few, if any, effective therapies exist," said Geoffrey Duyk, M.D., Ph.D., Co-founder and CEO at Grove. "We believe our Bionic Biologics platform represents a true paradigm shift for drug development, enabling us to rapidly develop molecules that can selectively inhibit or degrade even the most challenging intracellular drug targets. We are deeply grateful to our seed and Series A investors for their ongoing confidence and support as we advance this exciting new technology to patients."

"Proteins are the molecular machines that drive all essential cellular function, and dysregulated intracellular protein-protein interactions are the cause of many human diseases," said Nathan Gianneschi, Ph.D., Scientific Founder of Grove Biopharma and Professor at Northwestern University. "Existing drug modalities are either unable to penetrate cells or cannot effectively engage these large disease target domains. Bionic Biologics provide a new approach to this challenge, and I am excited to continue collaborating with the Grove team to advance this new modality to the clinic."

Bionic Biologics provide a new approach to targeting protein-protein interactions (PPI), distinguished by the following key characteristics:

Bionic: Hybrid synthetic biomolecules with enhanced functionality beyond what is possible in nature.
Cell permeable: Multivalent, chameleonic architecture enables membrane permeability for reaching intracellular targets.
Customizable: Plug-and-play design, modular construction and tunable properties to rapidly develop and implement molecules, either monofunctional or bifunctional, against any target.
Grove Biopharma’s Bionic Biologics have been demonstrated in proof-of-concept studies across several validated yet formidable intracellular targets. The company’s pipeline is initially focused on oncology and neurodegenerative diseases, where the advantage of cell-permeability enables therapeutic intervention in these disease pathways. Grove’s lead effort is an androgen receptor signaling program for the treatment of castrate-resistant prostate cancer. Data to date has demonstrated in vivo proof-of-concept and the company is advancing towards an IND submission.

"Grove Biopharma is addressing one of the most important challenges in drug development — targeting intracellular protein-protein interactions—with a novel, synthetic biology-based approach," said Kiersten Stead, Ph.D., Managing Partner at DCVC Bio and Grove board member. "We believe the Bionic Biologics platform has the potential to unlock a whole world of new therapeutic possibilities," Stead highlights. "The combination of approaches Grove is taking will be used to pursue first in-class-medicines with exceptional profiles and ease of manufacturing."

The Grove Biopharma team brings together experienced industry leadership and deep expertise in chemistry, biology, and materials science. Originating from Professor Nathan Gianneschi’s lab at Northwestern University, the Bionic Biologics platform is now being advanced by the Grove Biopharma R&D team, including Paul Bertin, Ph.D., Co-Founder, President and Chief Technology Officer, and Robert Campbell, Ph.D., Chief Scientific Officer.

On April 23, 2025 Tempus AI, Inc. (NASDAQ: TEM), a technology company leading the adoption of AI to advance precision medicine and patient care, reported multi-year, strategic collaborations with AstraZeneca (LSE/STO/Nasdaq: AZN) and Pathos AI, Inc., in which the companies will work together to build a multimodal foundation model in oncology which can be used to gather biological and clinical insights, discover novel drug targets, and develop therapeutics for the broader oncology community (Press release, Tempus, APR 23, 2025, View Source [SID1234652081]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Tempus’ de-identified oncology data will be used to build the foundation model. Upon completion, the model will be shared among all three parties to advance their individual efforts to improve patient care. The agreements include $200 million in data licensing and model development fees to Tempus.

The agreement with AstraZeneca expands on the strategic partnership between the two companies announced in 2021 and aims to leverage Tempus’ AI-enabled platform and vast repository of multimodal data to advance novel therapeutic programs in oncology on a global scale.

"Generative AI and the emergence of large multimodal models is the final catalyst needed to usher in precision medicine in oncology at scale," said Eric Lefkofsky, Founder and CEO of Tempus. "Tempus has spent the last decade investing billions of dollars into collecting the necessary data needed for a foundation model of this kind to take shape. We look forward to working with AstraZeneca and Pathos to apply AI-enabled solutions to advance therapies in an effort to help patients live longer and healthier lives."

"Cancer drug discovery and clinical development are being transformed by the ability to analyze vast amounts of rich data using artificial intelligence," said Jorge Reis-Filho, Chief AI and Data Scientist, Oncology R&D, AstraZeneca. "We are excited to collaborate with Tempus and Pathos to advance our data and AI-driven R&D strategy through the development of a multimodal oncology foundation model that we believe will accelerate and increase the probability of clinical success across our diverse pipeline."

"As artificial intelligence becomes more prominent in drug discovery and development, the opportunity for companies like Pathos to build foundation models that seemed almost unimaginable a few years ago is now taking shape," said Mohamad Makhzoumi, Co-CEO of NEA and Pathos Board Member. "We couldn’t be more excited to collaborate with Tempus and AstraZeneca given the potential of these models to improve patient outcomes."