AMPLIA AND GARVAN INSTITUTE ENTER INTO COLLABORATION AGREEMENT

On June 28, 2021 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), a company developing new approaches for the treatment for cancer and fibrosis, reported that it has now finalised and executed a Collaboration Agreement and a Research & Licence Agreement with the Garvan Institute of Medical Research ("Garvan") in Sydney, Australia that was announced in March 2021 (Press release, Amplia Therapeutics, JUN 28, 2021, View Source;[email protected] [SID1234584386]). These Agreements define the structure of an ongoing collaborative research and clinical development program to be undertaken with Garvan which initially focuses on the use of Amplia’s FAK inhibitor, AMP945, to treat patients with pancreatic cancer.

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The collaboration, which was forecast with the signing of a non-binding Term Sheet in March 2021, provides Amplia with access to Garvan’s research strength in FAK biology and its extensive clinical research network. Already, non-clinical studies conducted in the laboratory of Professor Paul Timpson, Cancer Research Theme Leader at Garvan, a world-renowned expert in FAK biology, have provided Amplia with valuable insights into the ability of AMP945 to inhibit fibrosis and significantly improve survival in an animal model of aggressive pancreatic cancer. The Company is incorporating these insights and using its access to Garvan’s clinical research network to assist with the design and planning of a Phase 2 clinical trial of AMP945 in patients with pancreatic cancer that is scheduled to commence later this year. The terms of the final Collaboration Agreement also provide for expansion into other therapeutic areas.

Amplia’s CEO and Managing Director, Dr John Lambert, commented that "It is very exciting for Amplia to be able to tap into the extensive experience in FAK biology, cancer biology, and clinical networks that are available at a globally-recognised research institute such as Garvan. We have already seen the benefits of this collaboration through the results of the non-clinical studies which we announced earlier this year. These studies have provided important insights into the biology of AMP945 and have further validated our decision to progress this promising drug into a Phase 2 clinical trial in pancreatic cancer patients."

Professor Chris Goodnow, Garvan’s Executive Director noted that "At Garvan, we aim to translate our cancer research findings into better treatment options and improved clinical outcomes for patients. We are delighted to be working with Amplia in the development of its unique FAK inhibitors as potential new anti-fibrotic treatments for patients with pancreatic cancer or other fibrotic diseases."

Under the terms of the Collaboration Agreement, which has an initial term of 2 years, Amplia will receive first rights to participate in research projects relating to the use of FAK inhibitors in combination with other therapeutic products for the treatment of cancer. Under the terms of the Research and Licence Agreement, Amplia agrees to fund studies of the use of AMP945 in combination with gemcitabine / Abraxane for the treatment of cancer, with an initial focus on pancreatic cancer, and Amplia will receive first rights to new intellectual property arising from the collaboration.

This ASX announcement was approved and authorised for release by the Board of Amplia Therapeutics

Houston-Based Tvardi Therapeutics Raises $74 Million in Series B Funding

On June 27, 2021 Tvardi Therapeutics, a Houston biopharmaceutical company, reported that it had raised $74 million in a new round of financing that will send its drug candidates through mid-stage clinical trials for treatment of cancer and fibrosis (Press release, Tvardi Therapeutics, JUN 27, 2021, View Source [SID1234584511]). The company, founded in 2017, specializes in the development of STAT3 inhibitors, which induce death in cancer cells. Tvardi CEO Imran Alibhai said the latest round of funding will help the company move out of "stealth mode" and raise its public profile.

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"With this financing we are positioned to advance the clinical development" of the company’s drug candidates, Alibhai said. The money will also help the company to expand its workforce, he added. The company’s latest round of financing is known as Series B. Series B is the third round of fundraising for new companies that typically comes after the startups have met certain milestones in their growth.

Officials with the company say the key molecule used in its drugs, TTI-101, has been shown in early clinical studies to be well tolerated among patients and can shrink a broad range of tumors.

Innovent Announces the China NMPA Approval of TYVYT® (sintilimab injection) in Combination with BYVASDA® (bevacizumab biosimilar injection) as First-Line Therapy for People with Hepatocellular Carcinoma

On June 27, 2021 Innovent Biologics, Inc. (Innovent) (HKEX: 01801), a world-class biopharmaceutical company that develops, manufactures and commercializes high-quality medicines for the treatment of cancer, metabolic, autoimmune and other major diseases reported that the National Medical Products Administration (NMPA) of China has approved the supplemental New Drug Application (sNDA) for TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) as a first-line treatment for people with advanced or unresectable hepatocellular carcinoma (HCC). This is the first regulatory approval of a PD-1 inhibitor-based combination therapy for the first-line treatment for HCC.

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This is also the fourth NMPA-approved indication of TYVYT (sintilimab injection) as well as the fourth NMPA-approved indication of BYVASDA (bevacizumab biosimilar injection). TYVYT (sintilimab injection) was approved in China for the treatment of relapsed or refractory classical Hodgkin’s lymphoma in December 2018, the first-line treatment of nonsquamous non-small cell lung cancer (NSCLC) in February 2021, and the first-line treatment of squamous NSCLC in June 2021. BYVASDA (bevacizumab biosimilar injection) was previously approved for advanced non-small cell lung cancer, metastatic colorectal cancer, and adult recurrent glioblastoma.

This new approval was based on the results of a randomized, open-label Phase 3 clinical trial (ORIENT-32) of TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) as first-line therapy for unresectable HCC. Based on the interim analysis conducted by the Independent Data Monitoring Committee (IDMC), TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) demonstrated a statistically significant improvement in overall survival (OS) and progression-free survival (PFS) as assessed by Independent Radiographic Review Committee (IRRC) compared to sorafenib, meeting the pre-defined efficacy criteria. Safety analyses revealed no new safety signals. The ORIENT-32 results were published in The Lancet Oncology on June 15, 2021.

Professor Fan Jia from Zhongshan Hospital of Fudan University stated," In China, liver cancer is the second most common cause of cancer-related death and ranks fourth in terms of incidence with a five-year survival rate of only 10 percent. Response of hepatocellular carcinoma to chemotherapy and targeted therapy is undesirable, while immunotherapy has emerged as breakthrough treatment for hepatocellular carcinoma. The ORIENT-32 has demonstrated that sintilimab plus bevacizumab can extend the overall survival and progression-free survival in this patient population and bring significant clinical benefits. The approval will provide a new option for the first-line treatment of these patients with few systemic options, and also contribute to the ‘Healthy China 2030’."

Dr. Yongjun Liu, President of Innovent, stated: "Liver cancer is the third leading cause of cancer death globally, and China accounts for over 50 percent of all new cases and deaths worldwide. The disease is a serious threat to the life and health of Chinese people and a heavy burden on society and families, with hepatocellular carcinoma accounting for 85 to 90 percent of all liver cancer. We are very pleased that TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) – two drugs recognized by the China national innovation drug development project – is the first approved PD-1 inhibitor-based combination therapy for the first-line treatment of people with hepatocellular carcinoma. Innovent is proud to continue delivering on our mission of developing high-quality biopharmaceuticals that are affordable to ordinary people, while also contributing to the ‘Healthy China 2030’ Plan for cancer prevention and treatment."

About the ORIENT-32 Trial
ORIENT-32 is a Phase 3 randomized, open-label, multi-center study conducted in China to evaluate the efficacy and safety of TYVYT (sintilimab injection) in combination with BYVASDA (bevacizumab biosimilar injection) compared to sorafenib for the first-line treatment of patients with advanced hepatocellular carcinoma(ClinicalTrials.gov, NCT03794440). The primary endpoints of the trial were overall survival (OS) and progression-free survival (PFS) as assessed by Independent Radiographic Review Committee (IRRC) based on RECIST v1.1.

A total of 571 patients were enrolled and randomly assigned 2:1 to receive either TYVYT (sintilimab injection) plus BYVASDA (bevacizumab biosimilar injection) or sorafenib until disease progression or unacceptable toxicity. The combination therapy showed significant improvements in OS and PFS compared to sorafenib, and safety was consistent with previously reported safety profiles of each drug. The full results of ORIENT-32 were published in The Lancet Oncology on June 15, 2021.

About Hepatocellular Carcinoma
Primary liver cancer(PLC)is a common malignancy of the digestive system worldwide, among which about half of all new cases and deaths occur in China. The main pathological types of liver cancer are hepatocellular carcinoma (HCC), which accounts for 85 to 90 percent, and a small number of cases of intrahepatic cholangiocarcinoma(ICC)and HCC-ICC mixed liver cancer. In China, HCC is primarily caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection.

About Sintilimab
Sintilimab, marketed as TYVYT (sintilimab injection) in China, is an innovative PD-1 inhibitor with global quality standards jointly developed by Innovent and Eli Lilly and Company. Sintilimab is an immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1 / PD-Ligand 1 (PD-L1) pathway, and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies of sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials.

In China, sintilimab has been approved for four indications, including:

The treatment of relapsed or refractory classic Hodgkin’s lymphoma after two lines or later of systemic chemotherapy
In combination with pemetrexed and platinum chemotherapy, for the first-line treatment of nonsquamous non-small cell lung cancer
In combination with gemcitabine and platinum chemotherapy, for the first-line treatment of squamous non-small cell lung cancer
In combination with BYVASDA (bevacizumab biosimilar injection) for the first-line treatment of hepatocellular carcinoma
Additionally, Innovent currently has a regulatory submission under review in China for sintilimab for the second-line treatment of squamous non-small cell lung cancer.

Innovent also has two clinical studies of sintilimab that have met their primary endpoints:

In combination with cisplatin plus paclitaxel or cisplatin plus 5-fluorouracil for the first-line treatment of esophageal squamous cell carcinoma
The second-line treatment of esophageal squamous cell carcinoma
In May 2021, the U.S. FDA accepted for review the Biologics License Application (BLA) for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of nonsquamous non-small cell lung cancer.

Sintilimab was included in China’s National Reimbursement Drug List (NRDL) in 2019 as the first PD-1 inhibitor and the only PD-1 included in the list in that year.

About BYVASDA (bevacizumab biosimilar injection)
BYVASDA, also known as IBI305, is a bevacizumab biosimilar and a recombinant humanized anti-VEGF monoclonal antibody drug. Vascular endothelial growth factor (VEGF) is an important factor in angiogenesis that is highly expressed by the endothelial cells in most human tumors. An anti-VEGF antibody binds VEGF-A selectively with high affinity and blocks its binding to VEGF-2 receptors on the surface of vascular endothelial cells, thereby inhibiting signaling pathways such as PI3K-Akt/PKB and Ras-Raf-MEK-ERK. BYVASDA produces anti-tumor effects by inhibiting the growth, proliferation and migration of vascular endothelial cells, blocking angiogenesis, reducing vascular permeability, blocking blood supply to tumor tissues, inhibiting the proliferation and metastasis of tumor cells and inducing apoptosis in tumor cells. Since its launch, bevacizumab has been approved for the treatment of patients with multiple malignant tumors globally, including non-small cell lung cancer, metastatic colorectal cancer, glioblastoma, renal cell carcinoma, cervical cancer, and epithelial ovarian, fallopian tube, or primary peritoneal cancer. The efficacy and safety of bevacizumab in these tumor types have been well recognized worldwide.

In China, BYVASDA (bevacizumab biosimilar injection) is approved for indications including advanced non-small cell lung cancer, metastatic colorectal cancer, adult recurrent glioblastoma, and advanced or unresectable hepatocellular carcinoma. (Press release, Innovent Biologics, JUN 27, 2021, View Source [SID1234584387])

Alphageneron to Participate in the ROTH Virtual Healthcare Private Company Forum on June 28th, 2021

On June 25, 2021 Alphageneron Pharmaceuticals, Inc. ("Alphageneron" or the "Company"), a privately-held clinical-stage biopharmaceutical company developing autologous and allogeneic Natural Killer (NK) cellular and antibody therapeutics reported that Robert Brooks, JD, founder and Chief Executive Officer of Alphageneron, will participate in the ROTH Healthcare Private Company Forum to be hosted virtually on Monday, June 28, 2021 (Press release, Alphageneron Pharmaceuticals, JUN 25, 2021, View Source [SID1234584647]).

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Alphageneron’s CEO, Robert Brooks will speak on the Cancer Panel 2, entitled "Natural Killer Cell Approaches To Eradicate Tumors," as one of the presenting companies on the panel with "proof of concept" data utilizing NK cells against solid tumors. Mr. Brooks, will discuss a prior completed Phase IIa Clinical Trial with Advanced non-small lung cancer (NSCLC) patients, receiving autologous Hsp70 targeted NK Cell therapy (ENKASTIM), after radio-chemotherapy, in Germany. The Company is planning a Phase IIa Clinical Combination Trial with Advanced NSCLC patients receiving ENKASTIM and PD (L)-1 checkpoint inhibitors, after Standard of Care, in the United States. Alphageneron is also planning a Phase I clinical Combination trial with Metastatic Colorectal cancer with allogeneic donor genetically edited NK cell therapy, (ANKASTIM) in the United States.

Date: Monday January 28, 2021
Time: 12pm-1pm EDT

Entry into a Material Definitive Agreement

On June 25, 2021, Moleculin Biotech, Inc. ("Moleculin" or "Company"), repored that it entered into an At Market Issuance Sales Agreement (the "Agreement") with Oppenheimer & Co. Inc. (the "Agent") (Filing, 8-K, Moleculin, JUN 25, 2021, View Source [SID1234584385]). Pursuant to the terms of the Agreement, the Company may sell from time to time through the Agent shares of the Company’s common stock, par value $0.001 per share ("Common Stock"), with an aggregate sales price of up to $50.0 million (the "Shares") .

Any sales of Shares pursuant to the Agreement will be made under the Company’s effective "shelf" registration statement (the "Registration Statement") on Form S-3 (File No. 333-256627), which became effective on June 11, 2021, and the related prospectus supplement and the accompanying prospectus, as filed with the Securities and Exchange Commission (the "SEC") on June 25, 2021.

Under the Agreement, the Company may sell Shares through the Agent by any method that is deemed an "at the market offering" as defined in Rule 415 under the Securities Act of 1933, as amended (the "Securities Act").

Sales of the Shares, if any, may be made at market prices prevailing at the time of sale, subject to such other terms as may be agreed upon at the time of sale, including a minimum sales price that may be stipulated by the Company’s Board of Directors or a duly authorized committee thereof. The Company or the Agent, under certain circumstances and upon notice to the other, may suspend the offering of the Shares under the Agreement. The offering of the Shares pursuant to the Agreement will terminate upon the sale of Shares in an aggregate offering amount equal to $50.0 million, or sooner if either the Company or the Agent terminate the Agreement pursuant to its terms.

The Company will pay a commission to the Agent of 3.0% of the gross proceeds of the sale of the Shares sold under the Agreement and reimburse the Agent for certain expenses. The Company has also provided the Agent with customary indemnification rights. The Company is not obligated to make any sales of Common Stock under the Agreement.

The foregoing description of the Agreement is not complete and is qualified in its entirety by reference to the full text of the Agreement, a copy of which is filed as Exhibit 1.1 to this Current Report on Form 8-K and is incorporated herein by reference. The Agreement is also incorporated by reference into the Registration Statement.

A copy of the opinion of Schiff Hardin LLP relating to the legality of the shares of Common Stock issuable under the Agreement is filed as Exhibit 5.1 to this Current Report on Form 8-K and is also incorporated by reference into the Registration Statement.

The above disclosure shall not constitute an offer to sell or the solicitation of an offer to buy the securities discussed herein, nor shall there be any offer, solicitation, or sale of the securities in any state in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state.

Lincoln Park Capital Agreement

On June 25, 2021, the Company entered into a purchase agreement (the "Purchase Agreement") with Lincoln Park Capital Fund, LLC ("Lincoln Park"), pursuant to which Lincoln Park has committed to purchase up to $20.0 million of shares (the "Purchase Shares") of Common Stock. Concurrently with entering into the Purchase Agreement, the Company also entered into a registration rights agreement with Lincoln Park, pursuant to which it agreed to take certain actions relating to the registration under the Securities Act of the offer and sale of the total amount of Common Stock issuable and available for issuance and sale as Shares (defined below) under the Purchase Agreement (the "Registration Rights Agreement").

Offers and sales of Common Stock pursuant to the Purchase Agreement are being made under the Registration Statement on Form S-3 (File No. 333-256627), which became effective on June 11, 2021, and the prospectus supplement related thereto and the accompanying prospectus, as filed with the Securities and Exchange Commission (the "SEC") on June 25, 2021.

Beginning on the Commencement Date (as defined below) and thereafter, the Company has the right, in its sole discretion, to present Lincoln Park with a purchase notice (a "Regular Purchase Notice"), directing Lincoln Park to purchase up to 75,000 Purchase Shares (the "Regular Purchase Amount") (a "Regular Purchase"). The Regular Purchase Amount may be increased to up to 100,000 shares if the closing sale price of the Common Stock is not below $4.00 per share, and to up to 150,000 shares if the closing sale price of the Common Stock is not below $5.00 per share. The Company and Lincoln Park may mutually agree to increase the Regular Purchase Amount.

The Purchase Agreement provides for a purchase price per Purchase Share for each Regular Purchase (the "Purchase Price") equal to the lesser of:

• the lowest sale price of the Common Stock on the Nasdaq Capital Market on the purchase date of such shares; and

• the average of the three lowest closing sale prices for the Common Stock on the Nasdaq Capital Market during the ten consecutive business days ending on the business day immediately preceding the purchase date of such shares.

The purchase price of Regular Purchases, Accelerated Purchases and Additional Accelerated Purchases and the minimum closing sale price for a Regular Purchase will be adjusted for any reorganization, recapitalization, non-cash dividend, stock split, reverse stock split or other similar transaction occurring during the business days used to compute the purchase price.

The Company issued 107,788 shares of Common Stock to Lincoln Park as a commitment fee in connection with entering into the Purchase Agreement and may issue an additional 53,893 shares pro-rata when and if Lincoln Park purchases (at the Company’s discretion) the $20,000,000 aggregate commitment (the "Commitment Shares" and together with the Purchase Shares, the "Shares").

The aggregate number of Shares that the Company can issue to Lincoln Park under the Purchase Agreement may in no case exceed 5,686,041 Shares (subject to proportional adjustments for stock splits, reverse stock splits and similar events as described above), which number of Shares is equal to 19.99% of the outstanding shares of Common Stock immediately prior to the execution of the Purchase Agreement (the "Exchange Cap"), unless (i) stockholder approval is obtained to issue shares of Common Stock in excess of the Exchange Cap, in which case the Exchange Cap will no longer apply, or (ii) the average price of all sales of Purchase Shares to Lincoln Park under the Purchase Agreement equals or exceeds the lower of (i) the Nasdaq official closing price immediately preceding the execution of the Purchase Agreement or (ii) the arithmetic average of the five Nasdaq official closing prices for the Common Stock immediately preceding the execution of the Purchase Agreement, plus an incremental amount to take into account the issuance of the Commitment Shares to Lincoln Park under the Purchase Agreement, such that the transactions contemplated by the Purchase Agreement are exempt from the Exchange Cap limitation under applicable Nasdaq rules. In any event, the Purchase Agreement specifically provides that we may not issue or sell any shares of our Common Stock under the Purchase Agreement if such issuance or sale would breach any applicable rules or regulations of the Nasdaq.

The Purchase Agreement contains customary representations, warranties, covenants, closing conditions and indemnification and termination provisions. Sales under the Purchase Agreement may commence only after certain conditions have been satisfied (the date on which all requisite conditions have been satisfied, the "Commencement Date"), which conditions include the delivery to Lincoln Park of a prospectus supplement covering the shares of Common Stock issued or sold by the Company to Lincoln Park under the Purchase Agreement, the filing with The Nasdaq Stock Market of a Listing of Additional Shares notification with respect to the Shares and Nasdaq having raised no objection to the consummation of transactions contemplated under the Purchase Agreement, and the receipt by Lincoln Park of a customary opinion of counsel and other certificates and closing documents.

The Purchase Agreement may be terminated by the Company at any time, at its sole discretion, without any cost or penalty, by giving one business day notice to Lincoln Park to terminate the Purchase Agreement. Lincoln Park has covenanted not to cause or engage in any manner whatsoever, any direct or indirect short selling or hedging of the Common Stock. Although the Company has agreed to reimburse Lincoln Park for a limited portion of the fees it incurred in connection with the Purchase Agreement, the Company did not pay any additional amounts to reimburse or otherwise compensate Lincoln Park in connection with the transaction, other than the issuance of the Commitment Shares.

There are no limitations on use of proceeds, financial or business covenants, restrictions on future financings (other than restrictions on the Company’s ability to enter into variable rate transactions described in the Purchase Agreement), rights of first refusal, participation rights, penalties or liquidated damages in the Purchase Agreement. The Company may deliver Purchase Notices under the Purchase Agreement, subject to market conditions, and in light of its capital needs from time to time and under the limitations contained in the Purchase Agreement. Any proceeds that the Company receives under the Purchase Agreement are expected to be used for working capital and general corporate purposes.

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