On September 28, 2021 Artios Pharma Limited (Artios), a leading biotech company pioneering the development of novel small molecule therapeutics that target the DNA Damage Response process in order to treat patients suffering from a broad range of cancers, reported it has dosed the first patient in its Phase 1/2a study with its polymerase theta (Polθ) inhibitor, ART4215 (Press release, Artios Pharma, SEP 28, 2021, View Source [SID1234590357]). The Polθ project was originally in-licensed from Cancer Research UK in 2016 as part of the initial formation of Artios.

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The open label, multi-center study will assess the safety, tolerability, pharmacokinetics, and clinical activity of ART4215 administered orally as a monotherapy and in combination with other anticancer medicines in patients with advanced or metastatic solid tumors. The study will enroll up to 206 patients and will be conducted at multiple oncology centers across the USA and Europe. The trial is led by principal investigators Erika P. Hamilton, M.D., Director of the Breast Cancer and Gynecologic Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, and Timothy Yap, M.B.B.S., Ph.D., Associate Professor of Investigational Cancer Therapeutics and Medical Director of the Institute for Applied Cancer Science at The University of Texas MD Anderson Cancer Center. Interim safety and tolerability data is expected in 2022. Full details can be found at www.clinicaltrials.gov under the identifier NCT04991480.

Dr. Niall Martin, Chief Executive Officer at Artios, said: "The initiation of our Phase 1/2a study is an important milestone for Artios and the DNA Damage Response field in general, launching the first evaluation of a specifically designed Polθ inhibitor in the clinic. Polθ is an important tumor-specific DDR target which we believe has the potential to exploit certain genetic vulnerabilities of cancer cells with defective DNA repair processes, while sparing healthy tissue. We have brought forward to the clinic a new and exciting inhibitor class where preclinical data shows the possible clinical utility that a potent, selective Polθ inhibitor may have as a single agent in patients who have progressed on PARP inhibitors, in combination with PARP inhibition in PARPi naïve patients and in combination with DNA damaging therapies such as ionizing radiation and cytotoxic chemotherapy. The progress of ART4215 supports Artios’s approach to leverage our internal expertise in identifying promising new DDR targets, developing novel molecules, working with our collaborators at Cancer Research UK, and advancing these molecules into the clinic. It has been a very productive year at Artios with the execution of our $153M Series C financing in July and now the expansion of our clinical pipeline, building upon our ongoing clinical development of ART0380, an ATR inhibitor, and our collaborations with Merck KGaA and Novartis."

Principal Investigator for the trial, Dr. Erika P. Hamilton, Director of the Breast Cancer and Gynecologic Cancer Research Program, Sarah Cannon Research Institute at Tennessee Oncology, said: "I am encouraged by the preclinical data for ART4215 that demonstrates the molecule’s potential to address areas of high unmet need such as overcoming de novo and acquired resistance to PARP inhibitors and DNA damaging therapy. We look forward to advancing these important studies for an entirely new class of inhibitors for patients who need more effective treatment options."

ART4215 is the first selective, orally bioavailable, small molecule inhibitor of the Polθ polymerase domain to enter the clinic. Polθ, a DNA polymerase, is a tumor-specific DDR target involved in microhomology mediated end joining (MMEJ) that is overexpressed in many tumors and found in low levels in healthy tissue. Extensive preclinical studies have demonstrated that ART4215 has broad potential clinical utility, as described in Artios’s recent Nature Communications publication, Zatreanu et al., 2021.

On September 27, 2021 Aglaia Therapeutics, a biotechnology startup developing promising new therapies that can overcome resistance to current targeted therapies in cancer patients, reported the successful completion of a €4M ($4.7M) seed funding round (Press release, Ribonexus, SEP 27, 2021, https://ribonexus-project.com/wp-content/uploads/2022/11/2021-09-27_Aglaia-Therapeutics-EN-FINAL.pdf [SID1234628870]). Advent France Biotechnology (AFB) led the round, with the participation of Crédit Mutuel Innovation and Pierre Fabre. AFB also acted as co-founder, with Alejo Chorny, current operating partner at AFB, now appointed chief operating officer (COO) of Aglaia Tx. Leading European cancer centers Institut Curie and Gustave Roussy participated in the creation of the company.

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The proceeds of the funding will be used to prepare the preclinical development program required to identify the first candidate. Aglaia Tx aims to develop promising new oncology therapies with the goal of delivering best- and first- in class drugs that can restore sensitivity to current targeted therapies in cancer patients that became resistant to these treatments. The company established a pipeline of small molecules in oncology targeting the initiation of mRNA translation.

While targeted therapies have clearly improved cancer patient outcomes, global efficacy of these treatments decreases over time, with patients rapidly developing resistance to therapies. Moreover, even with therapies that lead to a complete response, small populations of cancer cells often survive treatments, driving cancer relapse, which remains one of the most challenging obstacles to effective treatments.

"Our goal is to dramatically improve the standard of care in cancer patients; by restoring sensitivity and avoiding resistance to current targeted therapies. We have assembled a strong team of drug developers, scientists and investors," said Alejo Chorny, COO of Aglaia Therapeutics. "With this seed investment, Aglaia Therapeutics is extremely well positioned to advance its preclinical programs in the coming years and select its first innovative program."

"Aglaia Tx is a good example of our entrepreneur-investor approach and we firmly believe that its work opens up the possibility of tackling relapses, one of the main unmet medical needs in cancer treatment today," said Matthieu Coutet, managing partner at AFB. "We are thrilled to bring together two leading European cancer institutes, Gustave Roussy and Institut Curie; to collaborate on this unique startup creation aimed at overcoming resistance in oncology targeted therapies."

A collaboration between Aglaia Therapeutics, Gustave Roussy, Institut Curie and the University of Strasbourg, for the validation of targets involved in certain types of cancer, will allow the startup to keep working with the research and clinical teams of Pr Caroline Robert, Dr Stéphan Vagner and Dr Laurent Desaubry.

On September 27, 2021 Cothera Bioscience reported that it has received approval from the U.S. Food and Drug Administration (FDA) to initiate a global multi-center phase 2 clinical trial to test PC-002, an inhibitor that targets MYC mutations, in combination with carboplatin and etoposide (PE) in patients with castration resistant and neuroendocrine prostate cancer (NEPC) (Press release, Cothera Bioscience, SEP 27, 2021, View Source [SID1234618851]).

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NEPC most frequently develops in patients with castration-resistant prostate adenocarcinoma following standard treatment with androgen receptor antagonists, other hormonal therapy or taxane-based chemotherapy. Clinically, NEPC is highly aggressive and metastasizes to visceral organs, such as the liver, much more avidly than prostate adenocarcinoma. MYC is overexpressed in the majority of NEPC and appears to be critical to the development of NEPC. Recent data indicate that NEPC occurs in approximately one out of six patients who develop progressive hormone-resistant prostate cancer. The incidence of treatment-related NEPC is expected to rise due to the prevalent use of hormonal therapies in prostate cancer.

PC-002 is a first-in-class small molecule drug targeting MYC- mutated tumors. With more than 50% of human cancers showing increased expression, MYC is regarded as one of the most important yet "undruggable" cancer targets. With a unique mechanism of action, PC-002 selectively induces MYC protein degradation and cell apoptosis in MYC-dependent tumors. PC-002 may potentially target multiple indications in cancers involving MYC dysregulation.

Dr. Vernon Jiang, Co-founder and EVP of Cothera Bioscience, said: "The FDA’s approval of PC-002 to initiate human phase 2 clinical trials in NEPC is another important milestone for Cothera. The team worked efficiently to file the IND and obtained approval expeditiously. We will continue our effort to launch and execute late-stage clinical trials for other cancer indications, bringing breakthroughs and better treatment options to more cancer patients."

On September 27, 2021 Chemomab Therapeutics Ltd. (Nasdaq: CMMB) ("Chemomab"), a clinical-stage biotech company focused on the discovery and development of innovative therapeutics for fibrotic and inflammatory diseases with high unmet need, reported a research collaboration with Leeds University to further study the role of CCL24 in the vascular damage associated with systemic sclerosis (SSc), a rare rheumatic disease with high morbidity and mortality (Press release, Chemomab, SEP 27, 2021, View Source [SID1234594670]). The collaboration will be led by Francesco Del Galdo, MD, PhD, Professor of Experimental Medicine at the University of Leeds and Head of the Scleroderma Program at the Leeds Musculoskeletal Biomedical Research Centre. Prof. Del Galdo is a recognized expert in the study of SSc and other rheumatic conditions.

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CCL24 is a soluble protein that has been shown to play a key role in mediating fibrotic and inflammatory processes that are the hallmark pathologies related to SSc. It is the novel target for Chemomab’s CM-101, a first-in-class, CCL24 neutralizing monoclonal antibody that Chemomab plans to assess in a Phase 2 trial in SSc patients beginning early next year. Chemomab has generated substantial mechanistic data related to CCL24-associated fibrosis and inflammation in SSc, as well as early data showing that CCL24 is potentially involved in the vascular damage associated with SSc. The partnership with Prof. Del Galdo will seek to provide additional insights into the mechanisms underlying CCL24-associated vascular damage and could also uncover additional application opportunities for CM-101.

"We are delighted to partner with Prof. Del Galdo and his team to further study how CCL24 contributes to the vascular damage in SSc," said Dr. Adi Mor, CEO of Chemomab. "They have developed state-of-the art models of vascular damage based on their large collection of SSc patient samples. At Chemomab, we have extensively studied how CCL24 causes fibrosis and inflammation in preclinical SSc models. This collaboration is expected to increase our understanding of the association between CCL24 and vascular damage using human samples, with the aim of helping guide future SSc registration trials and ultimately providing benefit to these patients who have no effective treatment options."

Prof. Del Galdo said, "Systemic sclerosis is a connective tissue disease caused by an unfortunate combination of fibrosis, inflammation and vascular damage. Because of the nature of the tissue damage caused by SSc, it remains one of the most severe autoimmune diseases, with a poor prognosis and very limited treatment options. Extensive preclinical studies indicate that CCL24 is an important mediator of fibrosis and inflammation. We welcome the opportunity to partner with Chemomab to better understand the role of CCL24 in causing the vascular damage that contributes significantly to the overall morbidity and mortality of SSc patients."

About Systemic Sclerosis

SSc, also known as scleroderma, is a rare autoimmune rheumatic disease characterized by fibrosis and inflammation of the skin, joints and internal organs, as well as vascular abnormalities. It predominantly affects women and is typically diagnosed when patients are between 30 and 50 years old. It is the most lethal of the systemic rheumatic diseases with a median survival of only 10 years. There is no approved disease modifying drug for SSc. There currently are an estimated 100,000 SSc patients in the US.

On September 27, 2021 Tvardi Therapeutics ("Tvardi") reported that Fierce Biotech has named it as one of 2021’s Fierce 15 biotechnology companies, designating it as one of the most promising early-stage biotechnology companies in the industry (Press release, Tvardi Therapeutics, SEP 27, 2021, View Source [SID1234590681]).

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"In 2020, we got to celebrate the best and brightest biotechs trying to dig the world out of the pandemic. Speaking with this year’s class of Fierce 15 winners showed us that not even a global pandemic can stop incredible innovations in medicine, and we’re on the cusp of some new breakthrough treatments that have continued apace despite unprecedented disruption last year," said Annalee Armstrong, Senior Editor of Fierce Biotech. "Slowing down was not an option for our 2021 Fierce 15 winners. From a biotech exploring a new type of viral vector for gene therapies to one trying to crack fibroblasts as a way to target resistant tumors, the Fierce Biotech team heard one thing in common: strong teams of scientists and professionals united in a goal to advance life-changing medicines. We’re proud to showcase this esteemed group of emerging biotechs to the world."

Tvardi (www.tvardi.com) is a clinical-stage biopharmaceutical company developing small molecule inhibitors of STAT3, a key regulatory molecule positioned at the intersection of signaling pathways critical to cancer, chronic inflammation, and fibrosis. The company’s lead product, TTI-101, is currently being studied in a Phase 1 trial of patients with advanced solid tumors who have failed all lines of therapy. To date, TTI-101 has been well-tolerated and demonstrated multiple durable radiographic objective responses in cancer patients treated with TTI-101 monotherapy.

Imran Alibhai, Ph.D., chief executive officer at Tvardi, added, "We are thrilled that Fierce has selected us for this honor. It not only validates the compelling clinical data we have generated but also our small and growing team of industry veterans, drug developers, and preeminent researchers that are bringing our transformative therapies to patients in need. I would also like to congratulate all awardees of this year’s Fierce 15 competition, as we are proud to join them in this accolade."

The Fierce 15 celebrates the spirit of being "fierce" – championing innovation and creativity, even in the face of intense competition. This is Fierce Biotech’s 19th annual Fierce 15 selection.

An internationally recognized daily report reaching a network of over 300,000 biotech and pharma industry professionals, Fierce Biotech provides subscribers with an authoritative analysis of the day’s top stories. Every year Fierce Biotech evaluates hundreds of early-stage companies from around the world for its annual Fierce 15 list, which is based on a variety of factors such as the strength of its technology, partnerships, venture backers and a competitive market position.