On October 26, 2022 Immutep Limited (ASX: IMM; NASDAQ: IMMP) ("Immutep" or "the Company"), a clinical-stage biotechnology company developing novel LAG-3 immunotherapies for cancer and autoimmune disease, reported that the Independent Data Monitoring Committee (IDMC) for the randomised, controlled Phase IIb TACTI-003 trial has reviewed initial safety data and recommended continuing the trial with no modifications (Press release, Immutep, OCT 26, 2022, View Source [SID1234622552]).

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TACTI-003 is evaluating eftilagimod alpha ("efti" or "IMP321"), in combination withMSD’s (Merck & Co., Inc., Rahway, NJ, USA) anti-PD-1 therapy KEYTRUDA (pembrolizumab) as a 1st line therapy in approximately 154 patients with head and neck squamous cell carcinoma (HNSCC).

The IDMC safety analysis included 47 patients enrolled in either cohort A or cohort B of the TACTI-003 trial. Subjects in cohort A (CPS ≥1) are randomized 1:1 to receive either efti plus pembrolizumab or pembrolizumab alone. Subjects in cohort B (CPS <1) receive a combination of efti and pembrolizumab. The IDMC also reviewed initial efficacy data, although this was not the primary focus of the analysis.

Immutep’s CSO and CMO Dr. Frédéric Triebel said, "We are very pleased with the IDMC’s recommendation. While early, this represents positive affirmation of the decision to move TACTI-003 into the 1st line setting for head and neck squamous cell carcinoma patients following the robust results and durable responses that efti in combination with pembrolizumab achieved in the 2nd line setting. Notably, the encouraging antitumour activity previously attained spanned the entire spectrum of PD-L1 expression, which is important as the majority of patients have lower PD-L1 levels and are in need of new approaches to fight cancer".

Currently, 53/154 patients (approximately 34%) have been recruited into the TACTI-003 trial, and recruitment is accelerating as further sites have been activated in Europe and the United States. Based largely on the promising data from Immutep’s Phase II TACTI-002 trial (KEYNOTE-798) in 2nd line HNSCC, Immutep was granted Fast Track designation by the FDA for efti in combination with pembrolizumab in April 2021 for 1st line treatment of recurrent or metastatic HNSCC. This designation provides Immutep with access to more frequent meetings and communications with the FDA, and potentially enables Rolling Review of a Biologic License Application. In addition, Fast Track designation may provide Accelerated Approval and Priority Review if relevant criteria are met, for efti in HNSCC.

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

About Eftilagimod Alpha (Efti)

Efti is Immutep’s proprietary soluble LAG-3 clinical stage candidate that is a first-in-class antigen presenting cell (APC) activator for the treatment of cancer, capitalising on LAG-3’s unique characteristics to stimulate both innate and adaptive immunity. Efti binds to and activates antigen presenting cells via MHC II molecules leading to expansion and proliferation of CD8+ (cytotoxic) T cells, CD4+ (helper) T cells, dendritic cells, NK cells, and monocytes. It also upregulates the expression of key biological molecules like CXCL10 that further boost the immune system’s ability to fight cancer.

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Efti is under evaluation for a variety of solid tumours including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and HER2–/HR+ metastatic breast cancer. Its favourable safety profile enables various combinations, including with anti-PD-[L]1 immunotherapy and/or chemotherapy. Efti has received Fast Track designation in 1st line HNSCC and in 1st line NSCLC from the United States Food and Drug Administration (FDA).

About TACTI-003

TACTI-003 is a Phase IIb clinical trial in 1st line head and neck squamous cell carcinoma (HNSCC). The study will evaluate efti in combination with MSD’s KEYTRUDA (pembrolizumab) as a 1st line therapy in metastatic or recurrent HNSCC patients with PD-L1 negative and PD-L1 positive (CPS >1) tumours. It will be a randomised, controlled clinical study in approximately 154 patients and will take place across Australia, Europe and the United States of America in up to 35 clinical sites.

The study will evaluate the safety and efficacy of efti in combination with pembrolizumab, compared to pembrolizumab alone in 1st line metastatic or recurrent HNSCC patients with PD-L1 positive (CPS >1) tumours (cohort A), and determine the efficacy and safety of efti plus pembrolizumab in patients with PD-L1 negative tumours (CPS <1) (cohort B). According to the current plans, about 130 patients in cohort A will be randomised 1:1 to receive either efti plus pembrolizumab or pembrolizumab alone. Subjects in cohort B (up to 24 patients) will receive a combination of efti and pembrolizumab. The primary endpoint of the study is Overall Response Rate (ORR) according to RECIST 1.1. Secondary endpoints include Overall Survival (OS) and Progression Free Survival (PFS). For more information about the Phase IIb trial, visit clinicaltrials.gov (NCT04811027).

On October 26, 2022 Race Oncology reported that The September quarter (Q1 FY 2023) was highlighted by the Race team’s development of an improved and novel formulation of the company’s lead drug, Zantrene which enables peripheral intravenous (IV) delivery (ASX Announcement: 28 September 2022) (Press release, Race Oncology, OCT 26, 2022, View Source [SID1234622548]). The manufacture of the new formulation (codenamed RC220) has been contracted to Societal (San Diego, CA, USA) with an expected delivery date of late Q2 CY 2023. This improved formulation provides additional IP patent protection through to 2043 and expands the drug’s potential market application in cancer.

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A second highlight was the initiation of the new m6 A RNA methylation pathway-targeted drug discovery program, in collaboration with Professor Martin Scanlon, through the Monash Fragment Platform (ASX Announcement: 27 September 2022). This utilises the latest NMR based fragment screening approach to identify novel drug fragments that can inhibit the m6 A RNA demethylases FTO and ALKBH5. The Race share buyback program continued through Quarter 1 FY 2023 with $1.2 million invested in the purchase and cancelation of 611,687 Race shares on-market at prices the Board viewed as opportunistic and in the shareholder’s interest utilising available capital excess to current committed programs. Race continues to progress its Three Pillar Strategy, capitalising on the opportunity of RNA therapeutics in cancer and cardioprotection provided by Zantrene.

Management commentary Race CEO Phillip Lynch said: "Our development update on the improved IV formulation is particularly important to future clinical trial plans, as well as to gains in IP and broader market utility for Zantrene." Race CSO Daniel Tillett said: "I am very proud of the work the Race preclinical team have undertaken in developing the new IV formulation. I know how much effort, hard work and lateral thinking has gone into solving the peripheral delivery problem, something the original developers of Zantrene were not able to accomplish. The value of this breakthrough will be revealed as we advance Zantrene in the clinic." Race Chairman John Cullity said: "In addition to the significant advances in formulation and trial planning through the quarter, a program of work was launched to further refine and Key events of the quarter 

On 27 September 2022, Race announced that it had contracted the Monash Fragment Platform (MFP) to complete a fragment-based screening program, aimed at discovering novel drugs that inhibit the m6 A RNA demethylases FTO and ALKBH5. This program may lead to new IP, solely owned by Race for molecules targeting cancer and other metabolic diseases.  On 28 September 2022 Race announced its researchers, led by Dr Benjamin Buckley, in collaboration with the University of Wollongong, had developed a new formulation of Zantrene that enables peripheral (arm or leg vein) intravenous (IV) delivery to patients. This formula provides clinicians with an easier to use alternative to the current central line formulation, adds new IP and is well suited to solid tumour application.Other news from the quarter  Chief Executive Officer (CEO) Phillip Lynch and Chief Scientific Officer (CSO) Daniel Tillett renewed their employee service agreements with Race from 1 September 2022.

The extended employment agreements retain the previously announced compensation (ASX Announcement: 12 April 2022) and continue unless terminated by the either of the employees or by Race on 3 months notice.
 Race scientists Professor Michael Kelso and Dr Daniel Tillett, in collaboration with researchers from the University of Newcastle were awarded $999,998 on 20 September 2022 by the Medical Research Future Fund (MRFF) for a grant entitled "Cardiovascular disease and cancer: identifying shared disease pathways and pharmacological management."
 From this quarter onwards, Race will share the Top 20 shareholder register to minimise individual shareholder requests and provide an additional level of transparency that shareholders have requested.
 Race CSO Dr Daniel Tillett purchased 107,868 shares on-market at an average price of $1.95 up to 5 October 2022. Dr Tillett is Race’s largest individual shareholder.
 The Race Annual General Meeting will be held on Thursday 24 November 12 pm, at The Press Room, Radisson Blue Hotel, 27 O’Connell Street, Sydney NSW.

The Race clinical team attended the Blood 2022 Meeting in Sydney from 14-17 September, the Annual Scientific Meeting of the Haematology Society of Australia and New Zealand, the Australian and New Zealand Society of Blood Transfusion and the Thrombosis and Haemostasis Society of Australia and New Zealand. The Race team presented at the Australian Microcap Investment conference in Melbourne on 18 October and held a briefing session, well attended by Melbournebased shareholders on 20 October. The company is grateful to all those shareholders and investors who made time to hear a progress update. Summary of cash flow and quarterly activity As of 30 September 2022, Race held cash and equivalents of $29.38 million, compared with $33.54 million on 30 June 2022. The net change in cash reserves of $4.16 million was used to fund continued research expenditure and product for trials at $2.24 million, and a further $1.24 million for the share buyback.

Listing rule 4.7C.3 Payments during the quarter to Related Parties amounted to $214k, comprising payments of salaries and superannuation to executive directors of $170k and board fees to non-executive directors of $43k. Shareholders by holding range Race is pleased to report that shareholders totalled 9,168 as of September 30, 2022, showing continued shareholder interest in Race’s progress.

On October 26, 2022 NovAccess Global Inc. (OTCQB:XSNX), a biomedical company developing novel immunotherapies for brain tumor patients, reported the approval of its application with the U.S. Food and Drug Administration (FDA) for Orphan Drug Designation (ODD) for TLR-AD1, a vaccine immunotherapy for the treatment of aggressive brain cancers, including glioblastoma and other high-grade gliomas (Press release, NovAccess Global, OCT 26, 2022, View Source [SID1234622476]).

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"Orphan Drug Designation is yet another timely milestone achieved by NovAccess Global as we prepare an Investigative New Drug (IND) application for FDA approval to start human clinical trials. We expect to submit the IND in the first half of 2023," said the Company’s Chief Executive Officer Dr. Dwain K. Irvin. "We are very pleased to have received this approval, and we believe the promise of our platform technology is underscored by the FDA expanding the scope of our original submission. This has been a team effort and I would like to congratulate our team for its ambitious and comprehensive efforts. The designation represents a critical step forward as we address an important and unmet healthcare challenge in the treatment of brain cancers."

"The FDA approval of our Orphan Drug application for TLR-AD1 is an important step forward," said Dr. Christopher Wheeler, President of StemVax Therapeutics, a wholly owned division of NovAccess Global, and served as Company’s lead in interactions with the FDA. "With Orphan Drug Designation status granted by the FDA, TLR-AD1 serves as our vanguard technology in our portfolio in the fight against cancer. It is our first in a platform of novel immunotherapy and innovative technology solutions we intend to bring to market in the service of cancer patients and their families across the globe. The special status afforded to us through the Orphan Drug Designation will enable an acceleration of the development of our therapies for new treatment options to treat a wide range of glioblastoma patients."

Dr. Wheeler continued, "Our therapeutic path involves a transformational process where tumor-killing immune responses for malignant glioma (MG) cells are higher than that of previous immunotherapies. This unique process involves the addition of proprietary substances to create a "cocktail" for more personalized treatment that substantially increases clinical benefits for patients. We look forward to advancing this novel immunotherapy into the clinic."

Glioblastoma is a form of aggressive brain cancer that annually impacts approximately 250,000 people globally and is on the rise in many countries, according to NovAccess scientists and published reports. The market data is more alarming, with glioblastoma accounting for approximately 50% of all malignant brain cancers diagnosed in the United States each year, and more than 10,000 Americans dying from this tumor type annually. Less than 5% of people with this cancer live longer than five years after their diagnosis. The global glioblastoma treatment market was estimated to be valued in excess of $2 billion in 2020, with projections for a compounded annual growth rate of more than 8% throughout the remainder of the decade.

The FDA’s Office of Orphan Products Development grants orphan designation status to investigational drugs and therapies addressing rare medical diseases or conditions that affect fewer than 200,000 people in the United States. Orphan drug designation provides benefits to drug developers which may include assistance in the drug development process, financial incentives to support clinical development, tax credits for clinical costs, exemptions from certain FDA fees and the potential for seven years of post-approval marketing exclusivity.

Sponsors seeking orphan drug designation for a drug must submit a request for designation to the FDA. Orphan drug designation is a separate process from seeking commercial approval or licensing, and the receipt of orphan drug designation status does not change the regulatory requirements or process for obtaining marketing approval from the FDA.

About TLR-AD1
TLR-AD1 is designed to activate anti-tumor immune responses against these brain tumors using immune-activating dendritic cells combined with the patient’s own tumor proteins. The resulting dendritic cell vaccines are matured with a proprietary combination of Toll-like receptor (TLR) adjuvants to boost their immune-activating potency beyond current vaccine preparations.

NovAccess Global expects to submit an Investigational New Drug (IND) application to the FDA for TLR-AD1 in the first half of 2023. In advance of the IND filing, the Company expects to announce a partnership with a clinical manufacturing organization for vaccine testing and production readiness for phase I-II clinical trials of TLR-AD1.

On October 26, 2022 ImmVira, a Shenzhen company that develops next-gen anti-cancer drug vectors, reported that has signed Series-C+ financing documents with the first batch of investors (Press release, Immvira, OCT 26, 2022, View Source [SID1234622468]). The company will keep the round open for as long as two months. It told investors that they can also invest at the same terms as those established by the lead investor and ImmVira. The C+ round was led by China Merchants China Direct Investments Limited with Lifebay and Unifortune Group participating.

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On October 26, 2022 Foghorn Therapeutics Inc. (Nasdaq: FHTX), a clinical stage biotechnology company pioneering a new class of medicines that treat serious diseases by correcting abnormal gene expression, reported that it will present new data across its protein degradation platform at Hanson Wade’s 5th Annual Targeted Protein Degradation Summit (Press release, Foghorn Therapeutics, OCT 26, 2022, View Source [SID1234622453]). Early clinical data from the ongoing Phase 1 study of FHD-609 in synovial sarcoma and preclinical data from a newly disclosed program targeting CREB binding protein (CBP) in EP300 mutated cancers reinforce Foghorn’s significant advancement across its protein degradation platform and pipeline.

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"These data highlight the broad and unique capabilities of our protein degradation platform, which is designed to optimize the selectivity, safety, efficacy and administration of our protein degraders," said Danette Daniels, Vice President of Foghorn’s protein degradation platform. "We demonstrate highly potent and specific degradation of BRD9 with FHD-609 and, more significantly, in vivo loss of BRD9 in patient solid tumors. Additionally, we are excited to announce our new protein degrader program, Selective CBP, which has potential broad therapeutic applications in cancer."
FHD-609 is a potent, selective, intravenously administered protein degrader of BRD9, a component of the ncBAF complex, initially being developed for synovial sarcoma and SMARCB1-loss tumors. Preclinical studies have demonstrated tumor growth inhibition in synovial sarcoma, a cancer genetically dependent on BRD9. Initial clinical data that will be presented today, from two patients in the study with metastatic synovial sarcoma treated with the same low dose of FHD-609 from the ongoing Phase 1 dose escalation study, show degradation of BRD9 in on-treatment metastatic tumor biopsies. Preclinical data also show exquisite selectivity with FHD-609, potentially avoiding the adverse effects associated with unwanted off-target degradation. Foghorn will also include preclinical data highlighting the development of an orally bioavailable BRD9 selective degrader, demonstrating capabilities for both oral and IV formulations.
During the conference, Foghorn will also disclose the addition of its selective CBP degrader targeting EP300 mutant cancers to its pipeline. The Selective CBP program is aimed at degrading the CREB binding protein and has potential in subsets of several cancers such as bladder, colorectal, breast, gastric and lung. Using selective CBP degraders, the program plans to exploit the synthetic lethal relationship it shares with its paralog EP300 to identify and treat those patients with EP300 mutated cancers. If successful, the Selective CBP program has the potential to provide a new therapeutic option for over 100,000 patients a year.

"These data we are presenting this week not only highlight the strength and growing capabilities of our platform, but further establish Foghorn as a leader in the protein degradation field," said Adrian Gottschalk, Foghorn CEO. "We look forward to presenting the initial safety and efficacy data from the ongoing FHD-609 Phase 1 dose escalation trial in synovial sarcoma in 2023."
For a copy of the presentation, please click here.
About FHD-609
FHD-609 is a potent, selective, intravenously administered protein degrader of BRD9, a component of the ncBAF complex. Preclinical studies have demonstrated tumor growth inhibition in synovial sarcoma, a cancer genetically dependent on BRD9. To learn more about the first-in-human clinical trial of FHD-609 in synovial sarcoma, please visit ClinicalTrials.gov.
About Synovial Sarcoma
Synovial sarcoma is a rare, often aggressive soft tissue sarcoma that originates from different types of soft tissue, including muscle or ligaments. Synovial sarcoma can occur at any age but is most common among adolescents and young adults. It represents around 5-10% of all soft tissue sarcomas, with ~800 new cases each year in the United States. Surgery remains the most effective treatment for synovial sarcoma, and there are limited therapeutic treatment options.