On March 17, 2022 BerGenBio ASA (OSE: BGBIO), a clinical-stage biopharmaceutical company developing novel, selective AXL inhibitors for severe unmet medical needs, reported the publication of a peer-reviewed article entitled "AXL targeting restores PD-1 blockade sensitivity of STK11/LKB1 mutant NSCLC through expansion of TCF1+ CD8+ T cells" in the journal Cell Reports Medicine (Press release, BerGenBio, MAR 17, 2022, View Source [SID1234610215]).

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The article reports on research that identifies AXL as a critical targetable driver of immune suppression in STK11/LKB1 mutated non-small cell lung cancer (NSCLC). Mutations in STK11/LKB1 in NSCLC occur in approximately 20% of patients and are associated with poor outcomes and limited response to immune checkpoint blockade, commonly utilized treatments for lung cancer.

This article and its accompanying material are accessible here:

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The research was led by Professor Rolf A. Brekken, in the Hamon Center for Therapeutic Oncology Research at theUT Southwestern Medical Center. The group introduced a STK11/LKB1 mutation into a preclinical murine model of lung adenocarcinoma, resulting in immune checkpoint blockade refractory tumors. The group posits that the lack of response occurred because the STK11/LKB1 mutated tumors lacked a specific population of immune cells (TCF1-expressing CD8+ immune T cells). This immune cell population was also reduced in human NSCLC tumors carrying STK11/LKB1 mutations.

Systemic inhibition of AXL by the BerGenBio molecule bemcentinib led to increased type I interferon secretion from AXL-expressing dendritic cells, resulting in expansion of the TCF1+ T cell population and restored therapeutic response to immune checkpoint blockade treatment. These results were observed in both an immunocompetent mouse model and in mice bearing human STK11/LKB1 mutant NSCLC tumors along with a humanized immune system. The paper also summarizes clinical data in NSCLC patients with identified STK11/LKB1 mutations receiving bemcentinib and immune checkpoint blockage (pembrolizumab), who demonstrated objective clinical response to combination therapy.

In November 2021 BerGenBio announced that the U.S. Food and Drug Administration (FDA) granted Fast Track designation for bemcentinib in combination with an anti-PD-(L)1 agent as a treatment for patients with STK11/LKB1 altered advanced/metastatic NSCLC patients without actionable mutations.

Martin Olin, Chief Executive Officer of BerGenBio, commented: "We are pleased to receive this strong preclinical validation of the potential role of bemcentinib to treat STK11/LKB1 mutated NSCLC patients. Data suggests that this significant patient population is underserved by current immune checkpoint blockade therapies, and we hope that the combination with bemcentinib can restore the immune response in these patients. The identification of a new druggable biomarker segment such as the STK11/LKB1 mutations may offer significant hope for improved patient outcomes in combination with the current standard of care therapies. We look forward to initiating a clinical trial this year to advance bemcentinib into development for this patient population."

On March 17, 2022 Alexion, AstraZeneca’s Rare Disease group, reported that it has entered into a settlement agreement with Chugai Pharmaceutical Co., Ltd. (Chugai), resolving all patent disputes between the two companies related to Ultomiris (ravulizumab) (Press release, AstraZeneca, MAR 17, 2022, View Source [SID1234610214]).

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In accordance with the settlement agreement, Alexion and Chugai have taken steps to withdraw patent infringement proceedings filed with US District Court for the District of Delaware and Tokyo District Court.

Marc Dunoyer, Chief Executive Officer, Alexion, said: "With this settlement, we will continue to advance our Ultomiris development programmes in new indications and focus on our mission to transform the lives of people affected by rare diseases."

Financial considerations
Under the terms of the agreement, Alexion will make a single payment of $775m in the second quarter of 2022, for which a charge will be recognised through the non-core P&L in the first quarter of 2022. No further amounts are payable by either party. The settlement does not impact AstraZeneca’s financial guidance for 2022.

Notes

Ultomiris patent proceedings
US
In November 2018, Chugai filed a lawsuit against Alexion in the Delaware District Court alleging that Ultomiris infringes US patent No. 9,890,377 held by Chugai. Upon issuance of US patent No. 10,472,623 in November 2019, Chugai filed a second lawsuit in the same court alleging that Ultomiris also infringes that patent. The two lawsuits were consolidated in December 2019.

Japan
In December 2018, Chugai filed a lawsuit in the Tokyo District Court against Alexion Pharma GK alleging that Ultomiris infringed two Japanese patents (Japanese Patent No. 4954326 and No. 641743) held by Chugai. Chugai’s complaint sought unspecified damages and certain injunctive relief. Also beginning in 2016, Alexion had challenged the validity of four of Chugai’s Japanese patents. The IP High Court in Japan had found these patents invalid. Chugai filed a correction of these patents with the Japanese Patent Office. The Japanese Patent Office found the corrected patents invalid, and Chugai appealed the Patent Office’s decision to the IP High Court in Japan.

Europe
Beginning in 2016, Alexion challenged the validity of five of Chugai’s European patents. One patent was maintained by the Opposition Division of the European Patent Office while four were revoked. Three of the five decisions by the Opposition Division have been appealed to the Boards of Appeal for the European Patent Office.

Ultomiris
Ultomiris (ravulizumab), the first and only long-acting C5 complement inhibitor, offers immediate, complete, and sustained complement inhibition. The medication works by inhibiting the C5 protein in the terminal complement cascade, a part of the body’s immune system. When activated in an uncontrolled manner, the complement cascade over-responds, leading the body to attack its own healthy cells. Ultomiris is administered intravenously every eight weeks or, for paediatric patients less than 20kg, every four weeks, following a loading dose. Ultomiris is approved in the US for the treatment of adults and children (one month of age and older) with PNH; in the EU for adults, as well as for children (with a body weight of 10kg or above) and adolescents with PNH who experience haemolysis with clinical symptom(s) indicative of high disease activity, as well as for individuals who are clinically stable after having been treated with Soliris for at least the past six months; and in Japan as a treatment for adults with PNH. It is also approved in the US for aHUS to inhibit complement-mediated thrombotic microangiopathy in adult and paediatric (one month of age and older) patients, in the EU for the treatment of adults and children with a body weight of at least 10kg with aHUS, as well as in Japan for adults and children with aHUS.

On March 16 2022 Terrapeutics Pharma ("Terrapeutics") and the Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) reported that they have reached a cooperation agreement to co-develop novel natural products that will be the basis for new drugs in two of the most challenging drug targets that are considered the "holy grail" of the pharmaceutical industry (Press release, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS) , MAR 16, 2022, View Source [SID1234650070]). The HIPS is a joint institution of the Helmholtz Centre for Infection Research (HZI) and Saarland University.

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Some of the most devastating diseases, such as infections with antibiotic resistant bacteria and RAS-driven cancers (pancreatic, colon, and more), are currently undruggable despite detailed knowledge of the underlying molecular mechanisms. While industry leaders agree that small bioactive molecules produced by microorganisms have a tremendous potential to solve this therapeutic challenge, current methodologies can test only 0.1% of their potential. The staggering 99.9% are unexplored and considered "dark matter" to pharma companies.

Under this collaboration, Terrapeutics will utilize its ground breaking technology to screen and select microorganisms that produce small molecule inhibitors targeted against resistant bacteria and oncogenic RAS. HIPS will utilize its expertise to isolate, characterize and optimize the newly discovered novel molecules for their use in humans.

Dr. Ariel Werman CSO & Co-Founder of Terrapeutics said: "This agreement represents an important milestone in Terrapeutics road to become a world leader in natural molecule-based drug discovery, focusing on undruggable targets. Our revolutionary technology, enables us to look at the 99.9% fraction of the naturally produced molecules that the pharmaceutical industry is blind to, and rapidly, selectively and accurately pick microorganisms that produce molecules that respond to specific drug targets. It is as if we are performing a high throughput screening against a specific drug target, using nature as our library of compounds"

Mr. Eddie Sadan CEO & Co-Founder of Terrapeutics added that "this is a strategic engagement with a world leading research institute in the field of natural molecules for Pharmaceutical use that leverages our innovative approach to this field together with HIPS outstanding capabilities and knowledge to solve two of the biggest challenges the pharmaceutical industry faces".

Prof. Dr. Rolf Muller, Managing Director at the HIPS, commented: "We are intrigued to jointly evaluate the potential of Terrapeutics technology for the isolation of bacteria producing specific natural products. If we can manage to specifically isolate those bacteria that make the compounds we are looking for, we can skip a very time- and cost-intensive part of the usual drug development process. This would bring us a big step forwards in the fight against antimicrobial resistance (AMR) and other diseases threatening global human health."

On March 16, 2022 Helix BioPharma Corp. (TSX: "HBP"), ("Helix" or the "Company"), a clinical-stage biopharmaceutical company developing unique therapies in the field of immuno-oncology based on its proprietary technological platform DOS47, reported fiscal 2022 second quarter results for the period ending January 31, 2022 (Press release, Helix BioPharma, MAR 16, 2022, View Source [SID1234611326]).

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On March 16, 2022 Pascal Biosciences Inc. ("Pascal" or the "Company") (TSXV:PAS) (OTC:PSCBF) (FSE: 6PB-FF). Pascal reported that it has signed a term sheet dated March 16, 2022 with Shape Capital Pty Ltd. of Melbourne, Victoria ("Shape"), an investment and advisory firm, which will provide a three-year, convertible note for $2,000,000 (Press release, Pascal Biosciences, MAR 16, 2022, View Source [SID1234610468]).

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The note is non-interest bearing and is structured to advance to Pascal tranches of $55,000 per month which, at the option of the investors in the note ("Investors"), can be doubled to $110,000 on any given month. At the company’s option the draw down can be paused for up to two periods of up to three months per period. With each drawdown Pascal will issue common shares ("Shares") to satisfy the note. The number of shares issued will be based on a Conversion Price equal to 90% of the average of five daily VWAPs, selected by the Investor, during the 22 trading days prior to the Conversion Notice. If that price is less than the Discounted Market Price, as defined by the TSX.V, the Conversion Price will be the Discounted Market Price. The Company is being charged an administration fee by Shape of $130,000 ($65,0000 within 3-days of acceptance, and $65,000 at twelve months), and a commitment fee of $80,000. The $210,000 will be paid by the issue of 2,100,000 Shares at deemed price of $0.10 per Share. Investors will be issued 2,200,000 Share purchase warrants ("Warrants") to acquire, for one year, one further Share. These Warrants will be distributed pro-rata with the tranche distributions during the first year and will be priced at a 100% premium to the conversion price of the underlying tranche.

The Notes are subject to the acceptance of the TSX.V. All Shares will have a hold period of four months and one day from the date of issue.

In addition to this convertible note, the Company is working on arranging a private placement of up to $1,000,000, by the issue of units at a price of $.08. Each unit consists of one Share and one Share purchase warrant to purchase one additional Share, at a price of $.15 per Share for a term of two years.

Dr. Brian Bapty, Pascal Biosciences CEO, stated "We are thankful for the support provided by Shape Capital in the form of the convertible note. The note is well structured to offset the majority of near-term forecast monthly expenses and, combined with the proposed private placement, allows some flexibility as we focus our research efforts on the strongest drug candidates to advance towards clinical trials. Using good science to add value to products in development is our goal, and the measure of our success should be share price appreciation. With this in mind, shareholders should anticipate going forward a leaner pipeline and efforts from Pascal to capture other aspects of the biotechnology value chain."