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Curis and Aurigene Announce Amendment of Collaboration for the Development and Commercialization of CA-170

On February 5, 2020 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported that it has entered into an amendment of its collaboration, license and option agreement with Aurigene Discovery Technologies, Ltd. (Aurigene) (Press release, Aurigene Discovery, FEB 5, 2020, View Source [SID1234554540]). Under the terms of the amended agreement, Aurigene will fund and conduct a Phase 2b/3 randomized study evaluating CA-170, an orally available, dual
inhibitor of VISTA and PDL1, in combination with chemoradiation, in approximately 240 patients with nonsquamous
non-small cell lung cancer (nsNSCLC). In turn, Aurigene receives rights to develop and commercialize CA-170 in Asia, in addition to its existing rights in India and Russia, based on the terms of the original agreement. Curis retains U.S., E.U., and rest of world rights to CA-170, and is entitled to receive royalty payments on potential future sales of CA-170 in Asia.

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In 2019, Aurigene presented clinical data from a Phase 2a basket study of CA-170 in patients with multiple tumor types, including those with nsNSCLC. In the study, CA-170 demonstrated promising signs of safety and efficacy in nsNSCLC patients compared to various anti-PD-1/PD-L1 antibodies.

"We are pleased to announce this amendment which leverages our partner Aurigene’s expertise and resources to support the clinical advancement of CA-170, as well as maintain our rights to CA-170 outside of Asia," said James Dentzer, President and Chief Executive Officer of Curis. "Phase 2a data presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) conference last fall supported the potential for CA-170 to serve as a therapeutic option for patients with nsNSCLC. We look forward to working with our partner Aurigene to further explore this opportunity."

"Despite recent advancements, patients with localized unresectable NSCLC struggle with high rates of recurrence and need for expensive intravenous biologics. The CA-170 data presented at ESMO (Free ESMO Whitepaper) 2019 from Aurigene’s Phase 2 ASIAD trial showed encouraging results in Clinical Benefit Rate and Prolonged PFS and support its potential to provide clinically meaningful benefit to Stage III and IVa nsNSCLC patients, in combination with chemoradiation and as oral maintenance" said Kumar Prabhash, MD, Professor of Medical Oncology at Tata Memorial Hospital, Mumbai, India.

Murali Ramachandra, PhD, Chief Executive Officer of Aurigene, commented, "Development of CA-170, with its unique dual inhibition of PD-L1 and VISTA, is the result of years of hard-work and commitment by many people, including the patients who participated in the trials, caregivers and physicians, along with the talented teams at Aurigene and Curis. We look forward to further developing CA-170 in nsNSCLC."

Entry into a Material Definitive Agreement

On February 5, 2020, Adhera Therapeutics, Inc. (the "Company") reported that it has entered into a Securities Purchase Agreement with the investor parties thereto (collectively, the "Investors") pursuant to which the Investors agreed to purchase: (i) original issue discount unsecured Convertible Promissory Notes (the "Notes"), issued at a 10% original issue discount, for a total purchase price of $499,950, and (ii) warrants to purchase up to such number of shares of the common stock of the Company ("Common Stock") as is equal to the product obtained by multiplying 1.75 by the quotient obtained by dividing (A) the principal amount of the Notes by (B) the then applicable conversion price of the Notes (the "Warrants"; and the foregoing offering of securities being referred to as the "Offering") (Filing, 8-K, Adhera Therapeutics, FEB 5, 2020, View Source [SID1234554158]).

The Company, which terminated its business operations and associated personnel in December 2019 as described in the Current Report on Form 8-K that the Company filed with the Securities and Exchange Commission on December 17, 2019, intends to use the proceeds of the Offering to continue its efforts to restructure the Company and to identify potential strategic transactions to enhance the value of the Company and its assets as such opportunities arise.

Pursuant to the Notes, the Company promises to pay the principal sum of the Notes to the respective Investor, or its permitted assigns (the "Holder"), on the date that is the six (6) month anniversary of the original issue date, or August 5, 2020 (the "Maturity Date"), or such earlier date as the Note is required or permitted to be repaid as provided thereunder, and to pay interest to the Holder on the aggregate unconverted and then outstanding principal amount of the Note in accordance with the provisions thereof. Interest shall accrue to the Holders on the aggregate unconverted and then outstanding principal amount of the Notes at the rate of 10% per annum, calculated on the basis of a 360-day year and shall accrue daily commencing on the original issue date until payment in full of the outstanding principal (or conversion to the extent applicable), together with all accrued and unpaid interest, liquidated damages and other amounts which may become due thereunder, has been made.

On or after May 5, 2020 until the Notes are no longer outstanding, the Notes shall be convertible, in whole or in part, at any time, and from time to time, into shares of Common Stock at the option of the noteholder. The conversion price shall be the lower of: (i) $0.50 per share of Common Stock and (ii) 70% of the volume weighted average price of the Common Stock on the trading market on which the Common Stock is then listed or quoted for trading for the prior ten (10) trading days (as adjusted for stock splits, stock combinations and similar events); provided, that if the Notes are not prepaid on or before May 5, 2020, then the conversion price shall be the lower of (x) 60% of the conversion price as calculated above or (y) $0.05 (as adjusted for stock splits, stock combinations and similar events). The conversion price of the Notes shall also be adjusted as a result of subsequent equity sales by the Company, with customary exceptions.

The exercise price of the Warrants shall be equal to the conversion price of the Notes, provided, that on the date that the Notes are no longer outstanding, the exercise price shall be fixed at the conversion price of the Notes on such date, with the exercise price of the Warrants thereafter (and the number of shares of Common Stock issuable upon the exercise thereof) being subject to adjustment as set forth in the Warrants.

Maxim Group LLC ("Maxim") served as placement agent in connection with the Offering. The Company intends to pay a placement fee to Maxim equal to 10% of the aggregate gross proceeds raised in the Offering.

UArizona Cancer Center Receives $6.9M Grant for Skin Cancer Prevention Study

On February 5, 2020 University of Arizona Cancer Center reported is developing new strategies to prevent and reduce the risk of squamous cell carcinoma, the second most-common form of non-melanoma skin cancer (Press release, University of Arizona, FEB 5, 2020, View Source [SID1234553939]).

Skin cancer is the most common malignancy worldwide, and one in three new cancers diagnosed is a form of skin cancer, according to the Skin Cancer Foundation. This amounts to about 5 million non-melanoma skin cancers in the United States each year.

Clara Curiel-Lewandrowski, M.D., director of the Cutaneous Oncology Program and co-director of the Skin Cancer Institute at the Cancer Center, is principal investigator for a five-year, $6.9 million grant from the National Cancer Institute (#P01CA229112), a unit of the National Institutes of Health.

"This award is both an endorsement of the scientific contributions made by the Skin Cancer Institute research team and a true opportunity to make new groundbreaking advances in skin cancer prevention and treatment," Curiel-Lewandrowski said. "This is a stamp of approval that says the University of Arizona Cancer Center is the place with quality and innovative approaches in skin cancer therapeutic prevention research nationwide."

The Program Project Grant will assess, in animal models and human studies, the importance of a novel immune protein known as TLR4, which is modulated by solar ultraviolet radiation. The second focus of the grant includes characterization of a cascade of messages within skin cells recently discovered by the team that are found to promote development of skin cancer after exposure to sunlight. An impactful aspect of the award relates to the formulation and testing of topical drugs – lotions and creams, for example – that effectively can inhibit the action of these proteins ultimately to prevent squamous cell carcinoma formation.

"We are one of the few institutions that has mastered both experimental and clinical studies that effectively mimic the effect of sunlight," Curiel-Lewandrowski said. "These models allow us to test drugs that can reproducibly and accurately stop or reverse the cellular damage caused by the sun through pilot and Phase 1 clinical trials.

"This highly integrated and translational research-based program project emphasizes the importance of a multidisciplinary and precision-medicine approach for the prevention of squamous cell carcinoma of the skin," Curiel-Lewandrowski continued. "These discoveries also can serve as a model to prevent other epithelial malignancies."

"Skin cancer is a great risk to many people, especially those of us in Arizona," said University of Arizona President Robert C. Robbins. "The talented, dedicated researchers at the Cancer Center understand the importance of identifying innovative approaches for skin cancer prevention and treatment, and it is a well-deserved honor for this team to receive this prestigious grant. It is important to discover the safest ways to ensure people significantly reduce their risk of skin cancer while enjoying all the sunshine that makes our beautiful state such a wonderful place to live."

The new funding is the latest award for Curiel-Lewandrowski and the Skin Cancer Institute team, which has been a leader in skin cancer research, treatment and prevention across Arizona and beyond.

"It is important that our community knows that our Skin Cancer Institute is here for them and that our aligned vision is to prevent and cure skin cancer through research, education and clinical care," Curiel-Lewandrowski said. "We have an exceptional team in place with a common mission: To eradicate skin cancer in Arizona by decreasing skin-cancer incidence, where late diagnosis is not an option, and no lives are lost due to this preventable disease."

Beam Therapeutics Announces Pricing of Initial Public Offering

On February 5, 2020 Beam Therapeutics Inc. (Nasdaq: BEAM), a biotechnology company developing precision genetic medicines through base editing, reported the pricing of its initial public offering of 10,588,236 shares of common stock at a public offering price of $17.00 per share (Press release, Beam Therapeutics, FEB 5, 2020, View Source [SID1234553921]). All of the shares are being offered by Beam Therapeutics. In addition, Beam Therapeutics has granted the underwriters a 30-day option to purchase up to an additional 1,588,235 shares of common stock at the initial public offering price, less the underwriting discounts and commissions. Beam Therapeutics’ common stock is expected to begin trading on The Nasdaq Global Select Market on February 6, 2020 under the ticker symbol "BEAM."

The gross proceeds of the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Beam Therapeutics, are expected to be approximately $180 million excluding any exercise of the underwriters’ option to purchase additional shares. The offering is expected to close on February 10, 2020, subject to the satisfaction of customary closing conditions.

J.P. Morgan, Jefferies and Barclays are acting as joint book-running managers for the offering. Wedbush PacGrow is acting as lead manager for the offering.

A registration statement relating to the shares being sold in this offering became effective by the Securities and Exchange Commission on February 5, 2020. The offering is being made only by means of a prospectus, copies of which may be obtained from J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: (866) 803-9204, or by emailing [email protected]; Jefferies LLC, 520 Madison Avenue, 2nd Floor, New York, NY 10022, Attention: Equity Syndicate Prospectus Department, by telephone at 877-821-7388 or by email at [email protected]; or Barclays Capital Inc., Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717, telephone: 1-888-603-5847, or email: [email protected].

This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

Tumor secreted ANGPTL2 facilitates recruitment of neutrophils to the lung to promote lung pre-metastatic niche formation and targeting ANGPTL2 signaling affects metastatic disease

On February 5, 2020 Oncotarget reported that tumor-derived ANGPTL2 stimulates lung epithelial cells, which is essential for primary tumor-induced neutrophil recruitment in lung and subsequent pre-metastatic niche formation (Press release, Oncotarget, FEB 5, 2020, View Source [SID1234553905]).

Lastly, they identified that a p63 isoform, Np63, drives a high level of ANGPTL2 secretion and pharmaceutical inhibition of ANGPTL2 signaling by a non-RGD-based integrin-binding peptide diminished metastatic load in lungs likely due to reduction of the lung pre-metastatic niche formation.

Dr. Hakan Cam from the Center for Childhood Cancer and Blood Diseases at Nationwide Children’s Hospital as well as the Department of Pediatrics at The Ohio State University in Columbus Ohio USA said in their Oncotarget paper, "Primary tumors selectively and actively modify potential sites of metastasis, even prior to dissemination"

For instance, neutrophils have been identified as facilitators of breast cancer metastasis and of lung cancer metastasis after UV-induced inflammation through tumor-secreted exosomal RNAs.

Here, the scientists set out to determine how tumor-derived factors might affect the activation of lung epithelial cells in ways that elicit pro-metastatic inflammatory responses and facilitate the formation of the pre-metastatic following the recruitment of neutrophils.

It is also well established that the induction of inflammation-related genes results in the activation of neutrophils and as described above a body of evidence suggesting that the recruitment of neutrophils promotes cancer metastasis.

Collectively, by using spontaneous metastatic models, they investigated whether tumor secreted ANGPTL2 induces inflammation on lung epithelial cells by activating alpha5beta1 receptor and recruiting neutrophils to the pre-metastatic niche.

The Cam Research Team concluded in their Oncotarget article that they investigated whether lung epithelial cells might be essential for primary tumor-induced neutrophil recruitment to lung and the role that these infiltrating cells play in osteosarcoma PMN formation using spontaneous metastatic models.