On November 14, 2024 Alector, Inc. (Nasdaq: ALEC), a clinical-stage biotechnology company pioneering immuno-neurology, reported that the Company has entered into a debt financing agreement with Hercules Capital, Inc. (NYSE: HTGC) for up to $50 million (Press release, Alector, NOV 14, 2024, View Source [SID1234648387]).

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"Alector is in a strong cash position with more than $457 million in cash and investments. This credit facility further enhances our financial strength and provides the Company with increased strategic and operational flexibility," said Marc Grasso, M.D., Chief Financial Officer of Alector. "We anticipate transformational data from both the AL002 INVOKE-2 Phase 2 trial and the latozinemab INFRONT-3 pivotal Phase 3 trial within our runway. This credit facility provides additional funding to advance our preclinical pipeline including our proprietary, versatile Alector Brain Carrier blood-brain barrier platform and programs."

Under the terms of the agreement, Alector drew an initial $10 million at closing. An additional $15 million is available at the Company’s request through June 30, 2026, with an additional $25 million available upon lender approval. The Company is under no obligation to draw funds in the future. The credit facility carries a low double-digit cost of capital.

"Hercules is pleased to enter into a strategic relationship with Alector as it advances its portfolio of assets aimed at treating neurodegenerative diseases," said Lake McGuire, Managing Director at Hercules Capital. "This capital commitment from Hercules seeks to help Alector deliver new therapeutic options to patients and further advance their novel and proprietary blood-brain barrier technology."

Alector’s cash, cash equivalents and investments were $457.2 million as of September 30, 2024. Excluding this $50 million credit facility, the Company believes that its current cash, cash equivalents and investments will be sufficient to fund its operations through 2026.

On November 14, 2024 Akari Therapeutics, Plc (Nasdaq: AKTX) reported the completion of the merger (the Merger) of Akari Therapeutics, Plc (the Company) and Peak Bio, Inc. (Peak Bio), creating an innovative biotechnology company with a broader focus in the advancement of multiple disease therapies (Press release, Akari Therapeutics, NOV 14, 2024, View Source [SID1234648381]). The combined entity will continue the two companies’ significant progress in the development of Antibody Drug Conjugates (ADCs) and advanced therapies for autoimmune and inflammatory diseases, including Geographic Atrophy (GA).

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"We have worked throughout this year to bring these two exciting companies together and are thrilled that we have finally completed the merger," said Samir Patel, MD, Akari’s Interim President & CEO. "Critically important, our post-merger, pro-forma financial statements, as released on Form 8-K, demonstrate shareholder equity sufficient to remedy our Nasdaq shareholder deficiency matter."

"We will immediately begin executing against the strategy we have announced for the combined entity, with specific focus on Antibody Drug Conjugate and Geographic Atrophy milestones over the next 12 months," continued Dr. Patel. "The combination of immediate capital provided by the PIPE financing and the available credit under the Equity Line of Credit (ELOC) will allow us to continue development on our lead assets, which have the potential to bring new treatment options to diseases with high unmet medical need."

"I am thrilled to be leading Akari into the future as the incoming Chairman," said Hoyoung Huh, MD, PhD, Chairman and Founder of Peak Bio. "We will fully leverage our current assets and programs to drive shareholder value, while aggressively seeking out new opportunities to bring forward therapies to alter the treatment paradigm in oncology, autoimmune and inflammatory diseases. I would also like to thank Akari’s outgoing Chairman, Dr Ray Prudo, for his dedicated service and continued support of the Company."

The Financing

The Company entered into a definitive agreement for a private placement financing with investors on November 13, 2024, pursuant to which the Company agreed to sell and issue an aggregate of 1,713,402 unregistered American Depository Shares (ADSs), each representing 2,000 of the Company’s ordinary shares, and Series C Warrants (the Warrants) to purchase up to 1,173,402 ADSs. The per unit price per ADS was $1.70 for all investors other than insiders and $2.385 for insiders, which is equal to the consolidated closing bid price of the ADSs on The Nasdaq Stock Market on November 12, 2024 plus $0.125. The warrants have a term of 3 years from the closing date of the private placement, have cashless exercise provisions and, other than those issued to insiders which are exercisable immediately upon issuance, are exercisable beginning on the date that is six months after the Closing Date. All warrants have an exercise price of $2.26 per ADS, which is equal to the Nasdaq official closing price of the Company’s ADSs on the Nasdaq Capital Market on November 12, 2024.

The Company expects the private placement to close shortly after the merger subject to the satisfaction of customary closing obligations.

Paulson Investment Company LLC acted as placement agent for the financing. Chardan acted as an advisor for the merger and the Company has retained Chardan for future financing.

The securities described above were offered and sold in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the Act) and Regulation D promulgated thereunder and have not been registered under the Act or state securities laws and may not be offered or sold in the United States absent registration with the Securities and Exchange Commission or an applicable exemption from such registration requirements.

The Equity Line of Credit

Additionally, on November 13, 2024, the Company entered into a term sheet for a $50m equity line of credit (ELOC) with White Lion Capital, LLC (White Lion). Under the ELOC, the Company would have the right, but not the obligation, to sell White Lion up to $50m of newly issued ADSs over a 3-year period, subject to conditions including the filing and effectiveness of a resale registration statement with the SEC covering the resale of ADSs sold to White Lion. Upon execution of the ELOC, sales of ADSs to White Lion under the ELOC would depend on a variety of factors to be determined by the Company from time to time, including, among others, market conditions, the trading price of the ADSs and determinations by the Company as to the appropriate sources of funding and the Company’s operations.

On November 14, 2024 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapiesfor cancer and autoimmune disease, reported the presentation of new data from EFTISARC-NEO, a Phase II investigator-initiated trial of eftilagimod alpha (efti) in combination with radiotherapy plus KEYTRUDA (pembrolizumab) for patients with soft tissue sarcoma (STS), at the Connective Tissue Oncology Society (CTOS) 2024 Annual Meeting (Press release, Immutep, NOV 14, 2024, View Source [SID1234648305]). Based on preliminary analysis among 21 patients available for primary endpoint assessment, the triple combination therapy demonstrates significant efficacy in the neoadjuvant setting for resectable STS.

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Katarzyna Kozak, M.D., Ph.D., and Paweł Sobczuk, M.D., Ph.D., medical oncologists at the Department of Soft Tissue/Bone Sarcoma and Melanoma at MSCNRIO (Warsaw) and the trial’s principal investigators, stated: "Our belief in efti’s unique mechanism of action to complement radiotherapy and pembrolizumab in order drive better outcomes for patients with this rare aggressive disease was the foundation of the EFTISARC-NEO trial. These very encouraging results we are presenting today build our confidence in the synergistic effects of this new therapeutic approach and its potential to treat these patients in dire need of more effective therapies. In particular, the high level of hyalinization/fibrosis achieved with this novel combination therapy, three-times above historical results from standard radiotherapy, demonstrates remarkable efficacy in patients with resectable soft tissue sarcomas."

In the neoadjuvant setting for patients with resectable STS, the combination achieved a greater than threefold increase in tumour hyalinization/fibrosis (median 50%) at the time of surgical resection as compared to a historical median 15% from standard radiotherapy alone. In addition to being the primary endpoint of the EFTISARC-NEO study, the tumour hyalinization/fibrosisrate has also been identified as an important predictor of overall survival for STS patients.

The EFTISARC-NEO trial, with a data cut-off of 20 October 2024, also showed 71.4% of patients achieved a pathologic response defined as ≥35% of hyalinization/fibrosis and 9.5% of patients achieved a complete pathologic response. The triple combination therapy is safe with no grade ≥3 toxicities related to efti and pembrolizumab.

Dr. Frédéric Triebel, CSO of Immutep, said: "We are pleased with the strength of these preliminary results in this difficult-to-treat cancer. To see 71.4% of soft tissue sarcoma patients achieving a pathologic response defined as ≥35% of hyalinization/fibrosis combined with low viable tumour cells at 8% is very promising, especially as strong efficacy has been observed in different STS subtypes. We look forward to further evaluation of efti’s potential as neoadjuvant immunotherapy to help drive improved clinical outcomes.

The ongoing open-label EFTISARC-NEO Phase II study, conducted by the Maria Skłodowska-Curie National Research Institute of Oncology (MSCNRIO) in Warsaw, is expected to reach the planned enrolment of 40 patients in Q1 CY2025. The trial is primarily funded with an approved grant from the Polish government awarded by the Polish Medical Research Agency program. For more information, visit clinicaltrials.gov (NCT06128863)

On November 13, 2024 GSK plc (LSE/NYSE: GSK) reported positive headline results from a planned interim analysis of the DREAMM-7 head-to-head phase III trial evaluating Blenrep (belantamab mafodotin) in combination with bortezomib plus dexamethasone (BorDex) as a second-line or later treatment for relapsed or refractory multiple myeloma (Press release, GlaxoSmithKline, NOV 14, 2024, View Source [SID1234648299]). The trial met the key secondary endpoint of overall survival (OS), showing that belantamab mafodotin when combined with BorDex significantly reduced the risk of death versus standard of care daratumumab plus BorDex.

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Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK, said: "The overall survival results from the DREAMM-7 trial underscore the potential for this Blenrep combination to extend the lives of patients with relapsed/refractory multiple myeloma. This is a statistically significant and clinically meaningful advancement for patients and potentially transformative for treatment. We look forward to sharing these data with health authorities and presenting the full results at next month’s American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting."

Results from the interim analysis, including safety data, will be presented at the upcoming 66th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on 9 December 2024 at 11:15 a.m. PT.

The DREAMM (DRiving Excellence in Approaches to Multiple Myeloma) clinical development programme continues to evaluate the potential of belantamab mafodotin in early lines of treatment and in combination with novel therapies and standard of care treatments. In addition to DREAMM-7, this includes the ongoing head-to-head phase III DREAMM-8 trial evaluating belantamab mafodotin in combination with pomalidomide and dexamethasone versus bortezomib in combination with pomalidomide and dexamethasone.

A phase III study in newly diagnosed transplant ineligible multiple myeloma is expected to be initiated by the end of 2024 as part of the DREAMM programme.

In 2024, belantamab mafodotin combinations have been filed in the US, European Union1, Japan2, United Kingdom, Canada and Switzerland for the treatment of relapsed or refractory multiple myeloma based on the results of the DREAMM-7 and DREAMM-8 trials. In China3, the National Medical Products Administration has granted Breakthrough Therapy Designation for belantamab mafodotin in combination with BorDex, as well as priority review for the regulatory application based on the results of DREAMM-7.

About DREAMM-7
The DREAMM-7 phase III clinical trial is a multicentre, open-label, randomised trial evaluating the efficacy and safety of belantamab mafodotin in combination with BorDex compared to a combination of daratumumab and BorDex in patients with relapsed/refractory multiple myeloma who previously were treated with at least one prior line of multiple myeloma therapy, with documented disease progression during or after their most recent therapy.

A total of 494 participants were randomised at a 1:1 ratio to receive either belantamab mafodotin in combination with BorDex or a combination of daratumumab and BorDex. Belantamab mafodotin was scheduled to be dosed at 2.5mg/kg intravenously every three weeks.

The primary endpoint is PFS as per an independent review committee. The key secondary endpoints include OS, duration of response (DOR), and minimal residual disease (MRD) negativity rate as assessed by next-generation sequencing. Other secondary endpoints include overall response rate (ORR), safety, and patient reported and quality of life outcomes.

Results from DREAMM-7 were first presented4 at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Plenary Series in February 2024, shared in an encore presentation at the 2024 ASCO (Free ASCO Whitepaper) Annual Meeting, and published in the New England Journal of Medicine.

About multiple myeloma
Multiple myeloma is the third most common blood cancer globally and is generally considered treatable but not curable.5,6 There are approximately more than 180,000 new cases of multiple myeloma diagnosed globally each year.7 Research into new therapies is needed as multiple myeloma commonly becomes refractory to available treatments.8

About Blenrep
Blenrep is an antibody-drug conjugate comprising a humanised B-cell maturation antigen monoclonal antibody conjugated to the cytotoxic agent auristatin F via a non-cleavable linker. The drug linker technology is licensed from Seagen Inc.; the monoclonal antibody is produced using POTELLIGENT Technology licensed from BioWa Inc., a member of the Kyowa Kirin Group.

Blenrep is approved as monotherapy in Hong Kong, Israel and Singapore. Refer to the local Summary of Product Characteristics for a full list of adverse events and complete important safety information.

On November 13, 2024 TAE Life Sciences (TLS), TAE Life Sciences, in collaboration with Kyoto University and Principal Investigator Dr. Fuyuhiko Tamanoi, reported groundbreaking preclinical results in Boron Neutron Capture Therapy (BNCT). Utilizing TAE Life Science’s novel boron-10 drugs and Kyoto University Research Reactor (KURR) neutron source has generated significant pre-clinical data that may redefine the potential of BNCT in cancer treatment (Press release, TAE Life Sciences, NOV 13, 2024, View Source [SID1234649553]).

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Recently published in the Journal of Medicinal Chemistry (J. Med. Chem. 2023, 66, 13809−13820) and complemented by a newly submitted manuscript to ACS Central Science, our
research highlights a remarkable phenomenon known as the abscopal effect. This effect, where localized radiation treatment results in the shrinkage of tumors at untreated sites, holds profound implications for treating metastatic and micro-metastatic cancer.

In a key study using immune-competent balb/c mice, BNCT treatment of subcutaneous tumors on one leg completely inhibited tumor growth when the same tumor cells were reintroduced to the opposite leg two weeks post-treatment. These results, some of the most impressive preclinical data seen to date, suggest that BNCT can stimulate an immune response capable of generating memory cells to prevent tumor recurrence at distant sites.

"In one experiment, a mouse colon tumor was grown in the leg of a mouse and a second tumor was grown in its shoulder. BNCT was applied to the tumor in the leg, while the shoulder tumor was shielded from treatment. Remarkably, the untreated shoulder tumor exhibited a 34% reduction and slower growth rate compared to the control group, highlighting a potential systemic effect of BNCT."

"While the abscopal effect is not new in radiation oncology, these results with BNCT represent a significant step forward", said Dr. Sunil Krishnan, Radiation Oncologist and Professor at the Center for Translational Cancer Research at UT Health Houston. "What’s particularly exciting is that this level of immune response and tumor control has not traditionally been observed with standard x-ray-based radiation therapy. It underscores the potential for BNCT to not only address
primary tumors but also impact metastatic disease in a way we haven’t seen before."

Further investigations are underway to explore the mechanisms behind these results, focusing on the role of dendritic cells, T-cells, and macrophages in immune memory. Additionally, TAE Life Sciences is evaluating the combination of BNCT with immune checkpoint inhibitors, such as anti-CTLA4, anti-PD1, and anti-PDL1, to enhance outcomes in tumors with both "hot" (active immune profile) and "cold" (inactive immune profile) immune phenotypes.

"We are excited to demonstrate both the vaccine effect and the abscopal effect in preclinical BNCT experiments," said Kendall Morrison, Chief Scientific Officer at TAE Life Sciences.
"This research reinforces BNCT’s potential not only as a localized therapy but also as a treatment capable of addressing metastatic cancer. Combining BNCT with immunotherapy agents could significantly transform cancer treatment outcomes."

If these preclinical results can be translated to clinical applications, it could pave the way for improved responses to immune checkpoint blockade therapies, particularly for challenging "cold" tumors.