Akamis Bio Announces $60 Million in Funding Linked to Series A Prime Financing and New Strategic Partnership

On December 17, 2024 Akamis Bio, a clinical-stage oncology company using a proprietary Tumor-Specific Immuno-Gene (T-SIGn) therapy platform to deliver novel immunotherapeutic proteins, biomolecules and transgene combinations to treat solid tumors, reported $60 million in funding linked to the close of a Series A Prime financing round and entry into a strategic partnership for the development of its lead clinical candidate, NG-350A (Press release, Akamis Bio, DEC 17, 2024, View Source [SID1234649185]).

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The new funding will support the company’s work to advance NG-350A through a Phase 1b clinical proof-of-concept (PoC) study in patients with locally advanced rectal cancer (LARC). NG-350A is an intravenously delivered, transgene-armed tumor gene therapy designed to drive intratumoral expression of a CD40 agonist monoclonal antibody in both primary and metastatic epithelial-derived solid tumors. The Phase 1b PoC study, known as FORTRESS (NCT06459869), will evaluate clinical complete response (cCR) rates to NG-350A in combination with chemoradiotherapy (CRT) in adult patients with LARC and at least one risk factor for local or distant recurrence.

The Series A Prime financing was led by Sedgwick Yard, a global biotech venture capital firm with Greater China roots. In a separate transaction, Akamis Bio entered into a licensing agreement granting Xuanzhu Biopharma the Greater China Region Rights to NG-350A. Under the terms of the licensing agreement, Akamis Bio is eligible to receive undisclosed upfront payments plus regulatory and sales milestones, as well as tiered royalties in the high single- to low double-digit range on Greater China Region NG-350A sales.

"We are grateful for this strong vote of confidence in NG-350A, the T-SIGn platform and the Akamis Bio team. The Sedgwick Yard-led Series A Prime financing and Xuanzhu Biopharma licensing deal demonstrates our shared commitment with these partners to rapidly advancing NG-350A while also demonstrating the broader potential of T-SIGn," said Howard Davis, PhD, CEO of Akamis Bio. "Compelling clinical data from our prior studies have shown the consistent safety profile of T-SIGn, as well as the potential of intravenously-delivered NG-350A to drive sustained transgene expression capable of altering the tumor microenvironment. Our aim over the next 12-18 months is to deliver clinical proof-of-concept data for NG-350A via the FORTRESS study."

"We believe T-SIGn offers a true platform approach and that NG-350A is just the beginning of what we anticipate will become a robust pipeline of IV-delivered, tumor-targeted immunotherapies. We are very confident in the scientific and drug development acumen of the Akamis Bio management team, as well as in their ability to deliver on this opportunity to advance the standard of care for patients with difficult to treat solid tumors," said Richard Shen, Managing Director, Sedgwick Yard.

A recently published paper in the Journal for ImmunoTherapy of Cancer (JITC), described data from the FORTITUDE first-in-human dose escalation study in patients with metastatic/advanced epithelial tumors that provided initial proof-of-mechanism for NG-350A and highlighted the advantages of its intravenous route of administration. These data demonstrated the consistent safety profile of NG-350A, as well as providing strong evidence of tumor-selective delivery, replication and transgene expression. Additionally, this study demonstrated that intravenous delivery of NG-350A results in a superior overall pharmacokinetic and pharmacodynamic profile, with no apparent disadvantages versus intratumoral injection.

"We are thrilled to partner with Akamis Bio to develop and commercialize NG-350A in the Greater China Region. The T-SIGn platform has the potential to revolutionize the treatment of advanced metastatic solid tumors, and we look forward to working closely with the Akamis Bio team to bring this novel tumor gene therapy to patients," said Jiakui Li, PhD, CEO of Xuanzhu Biopharma.

Linked to the close of the Series A Prime financing, Akamis Bio added two new members to its Board of Directors: Richard Shen, Managing Director, Sedgwick Yard, and Adrian Chan, Managing Director, Sedgwick Yard.

About T-SIGn

Akamis Bio’s T-SIGn therapeutics are based on a replication competent, chimeric group B adenovirus backbone which has been adapted via directed evolution to home specifically to both primary and metastatic epithelial-derived solid tumor tissue following intravenous delivery. Once at the tumor site, T-SIGn therapeutics can drive the intratumoral expression of multiple transgene payloads, turning solid tumor cells into "drug factories" while leaving healthy tissue unaltered and intact. The intratumoral expression of immunologically active biomolecules and therapeutic proteins can result in the remodeling of the solid tumor microenvironment, triggering robust antitumor immune responses. T-SIGn therapeutics have the potential to be used in the monotherapy setting, as well as in combination with other immuno-oncology agents to target the key mechanisms that tumors use to evade the immune system.

A2A Pharmaceuticals, Inc. Announces Phase 1 Clinical Trial Advancements in TACC3 Inhibition Program Targeting Multiple Cancers

On December 17, 2024 A2A Pharmaceuticals, Inc. ("A2A" or "the company"), a clinical-stage pioneering biopharmaceutical company focused on developing innovative cancer therapies, reported progress in its clinical studies exploring TACC3 (Transforming Acidic Coiled-Coil 3) PPI inhibition in patients with ovarian cancer, triple-negative breast cancer (TNBC), and endometrial cancer (Press release, A2A Pharmaceuticals, DEC 17, 2024, View Source [SID1234649167]).

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A2A has progressed into cohort 4, an important inflection point in its Phase 1 clinical trial to assess the safety and efficacy of its lead TACC3 inhibitor, AO-252. Early results have shown strong safety profiles with the potential for a wide therapeutic index in these patient populations.

"We are excited about the advancements in our TACC3 program and its potential for patients with challenging cancer diagnoses. The company is continually exploring collaborations and partnerships to accelerate development timelines and enhance patient access to cutting-edge treatments," said Sotirios Stergiopoulos, M.D., CEO of A2A.

"While our current focus with AO-252 is on addressing the unmet needs in ovarian, TNBC, and endometrial cancers, we are equally excited about its potential to benefit patients in additional indications in the near future," added Robbin Frnka, Vice President of Clinical Operations."

The selected cancers are characterized by limited treatment options and high rates of recurrence in patients. A2A’s TACC3 PPI inhibitor is designed to disrupt critical cellular mechanisms involved in cancer cell proliferation, providing a much-needed new avenue of treatment for patients battling these aggressive malignancies.

"This trial represents a promising step forward in delivering therapies that could impact the standard of care for patients," said Alex Spira, M.D., principal investigator of Next Oncology Virginia. "A2A Pharmaceuticals shows dedication to supporting the cancer community by advancing novel therapies that target the underlying biology of tumors."

Beyond these indications, pre-clinical studies suggest A2A’s TACC3 PPI inhibitor may also show efficacy in other solid tumors, including gastric, prostate cancers, and sarcomas, etc. Ongoing research efforts are focused on expanding the indication spectrum and optimizing treatment regimens for diverse cancer types.

HighField Biopharmaceuticals Granted Clearance of IND in China for Clinical Trial of its Unique TRAFsomeTM T Cell Engager (HF50) To Treat Solid Tumor Cancers

On December 17, 2024 HighField Biopharmaceuticals, a clinical stage company using lipid-based therapeutics to treat cancer, diabetes and other diseases, reported that the Center for Drug Evaluation of China’s National Medical Products Administration has granted clearance of the company’s Investigational New Drug (IND) application to begin a clinical trial of HF50 in patients with advanced solid tumor cancers (Press release, HighField Biopharmaceuticals, DEC 17, 2024, View Source [SID1234649187]).

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"This is a highly significant milestone for our company and for patients," said Yuhong Xu, Ph.D., CEO and Scientific Founder of HighField. "HF50 is a T cell Redirecting Antibody Fragment-anchored Liposome, or TRAFsome, with two different antibodies attached; the first binds to T cells and the second binds to tumor cells. It is the first-of-its-kind liposomal T cell engager to emerge from our platform of immunoliposomes, and the first to enter clinical trials."

In addition to converting T cells into an army of cancer destroyers, HF50 also carries a payload that releases in the tumor microenvironment to facilitate the anti-tumor immune reactions.

The design of the TRAFsome T cell engagers builds upon the success of HighField’s LipoADCplexTM platform. The first product from this platform is K1, which contains the anti-HER2 antibody for binding to tumor cells and delivering cancer killing drugs. K1 is in clinical trials and has shown very good safety profiles in cancer patients.

"Once we proved the LipoADCplexTM platform could be safer, cheaper and more effective than ADCs (antibody-drug conjugates), the next logical step is to enlist immune cells with a second antibody to enable immunotherapy against the target cells," Dr. Xu explained. "T cell engagers can be very powerful. But over stimulation may result in high risk of toxicity and T cell exhaustion."

The Phase 1 open-label, dose escalation and dose expansion trial of HF50 will evaluate the safety, tolerability, pharmacokinetic characteristics, immunogenicity, and preliminary efficacy in patients with advanced solid tumors. The trial is expect to begin in 1Q2025.

"As a T cell engager, HF50 has advantages over bispecific antibody constructs and even CAR T cells," Dr. Xu said. "The liposomal T cell engagers can integrate three specific activities. The first is to activate T cells; the second is to direct the T cells to target cells; and the third is to release the payload to facilitate the immune responses."

Dr. Xu added, "The TRAFsomes can be made modularly with low costs. Preclinical data suggested they are much safer and more effective. We can also add different payloads to expand their application to other illnesses such as autoimmune diseases and illnesses related to aging."

Expert Systems Celebrates Milestone in Clinical Development of Lonitoclax, a Best-in-Class BCL-2 Inhibitor, Developed in Partnership with Lomond Therapeutics

On December 17, 2024 Expert Systems, a leader in AI-powered drug discovery, reported the promising clinical results of oral once-daily lonitoclax, a next-generation BCL-2 inhibitor developed in collaboration with Lomond Therapeutics (Press release, Lomond Therapeutics, DEC 17, 2024, View Source [SID1234649172]). The results of the single ascending dose Phase 1 studies demonstrate important advantages of lonitoclax over venetoclax and venetoclax-like molecules for chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and potentially other oncology indications.

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Lonitoclax demonstrated no significant safety signals at exposures sufficient to achieve robust inhibition of BCL-2, as measured via ex vivo activation of caspase in primary CLL cells. Importantly, the co-administration of itraconazole—a potent CYP 3A4 inhibitor—did not significantly alter lonitoclax exposures. These results highlight a key differentiation from venetoclax and similar molecules, which require complex dose titration and ritonavir co-administration, and emphasize important advantages in safety, tolerability, and feasibility of outpatient treatment.

"Lonitoclax’s promising Phase 1 results highlight the strength of our AI-enabled platform in driving the development of next-generation therapies," said Bill Farley, Chief Business Officer at Expert Systems. "Our platform de-risks early-stage drug development by reducing time and costs while delivering data-driven insights to optimize safety and efficacy. We are proud to support Lomond Therapeutics in advancing this innovative BCL-2 inhibitor, which has the potential to transform the treatment landscape for CLL and AML patients."

About Lonitoclax

Lonitoclax is a next generation BCL-2 inhibitor that has demonstrated best-in-class molecular pharmacology with the highest selectivity against BCL2, a key pro-survival protein that is overexpressed in many cancers. To mitigate the hematologic and immune toxicities observed with venetoclax, lonitoclax was designed with a unique binding mode to improve selectivity for BCL-2 over BCL-XL. In addition, a shorter half-life and reduced P4503A4 inhibition properties were built into the molecule to mitigate tumor lysis syndrome and drug accumulation risk, respectively. Lonitoclax has demonstrated monotherapy activity in pre-clinical models, as well as synergistic activity when combined with azacitidine, FLT3 inhibitors, and menin inhibitors in AML xenograft models. Unlike venetoclax, lonitoclax had minimal immunosuppressive activity on B cells, CD8 T cells, and NK cells in preclinical models.

IDEAYA Announces IDMC Recommendation of Move-Forward Dose in Part 2a of Registration-Enabling Trial of Darovasertib and Crizotinib Combination in 1L HLA-A2-Negative Metastatic Uveal Melanoma

On December 17, 2024 IDEAYA Biosciences, Inc. (Nasdaq: IDYA), a precision medicine oncology company committed to the discovery and development of targeted therapeutics, reported the Independent Data Monitoring Committee (IDMC) recommendation of a move-forward dose and the completion of the Part 2a dose optimization consistent with the U.S. Food and Drug Administration’s (FDA) Project Optimus guidelines for the potential registration-enabling Phase 2/3 trial evaluating the combination of darovasertib and crizotinib in the first-line (1L) setting in patients with HLA-A2-negative (HLA-A2(-)) metastatic uveal melanoma (MUM) (Press release, Ideaya Biosciences, DEC 17, 2024, View Source [SID1234649173]).

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"We are pleased with the recommendation of the IDMC and the selection of the move-forward dose for our potential registration-enabling trial evaluating the darovasertib and crizotinib combination in first-line HLA-A2(-) MUM patients. This allows us to complete the Part 2a portion of the study and seamlessly continue to enroll in Part 2b towards a potential accelerated approval based on the primary endpoint of median progression free survival," said Darrin M. Beaupre, M.D., Ph.D., Chief Medical Officer, IDEAYA Biosciences.

"The combination of darovasertib and crizotinib as first-line treatment has shown compelling preliminary clinical results in patients with HLA-A2(-) MUM. The IDMC recommendation of the move-forward dose supports the advancement of this potentially registration-enabling Phase 2/3 trial and is an important step in bringing a new treatment option to patients with MUM. Additionally, the continued rapid enrollment further validates the strong interest from physicians and patients, and highlights the significant unmet need in these patients, who historically have faced a poor prognosis," added Meredith McKean, M.D., MPH, Director, Melanoma and Skin Cancer Research at Sarah Cannon Research Institute, and clinical investigator on the potential registration-enabling clinical trial.

The darovasertib and crizotinib combination in MUM has FDA Fast Track designation and is currently being evaluated in two clinical trials: a potentially registration-enabling Phase 2/3 trial of darovasertib and crizotinib combination in first-line HLA-A2(-) MUM (NCT05987332) and a Phase 2 trial (NCT03947385). Additionally, darovasertib as neoadjuvant monotherapy is currently being evaluated in a Phase 2 trial in primary uveal melanoma (NCT05907954). IDEAYA is also finalizing a clinical trial protocol and is targeting to initiate a potential Phase 3 registration-enabling study for neoadjuvant uveal melanoma patients in the first half of 2025.