On November 12, 2021 Asher Biotherapeutics, a biotechnology company developing precisely-directed immunotherapies for cancer, autoimmune, and infectious diseases, reported new preclinical data demonstrating proof of concept for its cis-targeting platform and lead program AB248 (Press release, Asher Biotherapeutics, NOV 12, 2021, View Source [SID1234595460]). AB248 is an engineered intereukin-2 (IL-2) immunotherapy, designed to selectively target CD8+ effector T cells. The data will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 36th Annual Meeting (SITC 2021), being held in Washington D.C. and virtually, November 10-14, 2021.

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"We are pleased to share two presentations at SITC (Free SITC Whitepaper), providing further evidence that our cis-targeting approach enables us to craft exquisitely selective molecules, which activate only the desired immune cell types. This approach allows us to deliver immune activators to the cell types that drive efficacy, while avoiding other cell types that can lead to increased toxicities or other undesired consequences. These data provide further validation for our platform, which has now generated multiple lead molecules against high value targets and support our efforts to advance a pipeline of immunotherapies to provide better outcomes to patients," said Andy Yeung, Ph.D., Chief Technology Officer and Founder of Asher Bio.

Ivana Djuretic, Ph.D., Chief Scientific Officer and Founder of Asher Bio, added: "Historically IL-2 has proven to be a very potent immunotherapy capable of inducing durable complete responses in some cancer patients, but IL-2’s potential has been severely limited by toxicities, which arise due to non-selective activation of many different cell types. Our approach is to focus IL-2 to selectively activate CD8+ T cells, the primary immune cell subset that drives anti-tumor efficacy in response to IL-2 pathway activation. We are encouraged by the preclinical results presented at SITC (Free SITC Whitepaper), which demonstrate the potential for AB248 to deliver both enhanced anti-tumor efficacy and improved safety and reinforce our confidence in AB248’s potential as a best-in-class IL-2 immunotherapy. We look forward to advancing AB248 into clinical studies across multiple solid tumor types next year."

In an oral presentation titled, "CD8-targeted IL-2 drives potent anti-tumor efficacy and promotes action of tumor specific vaccines," Bob Schreiber, Ph.D., Professor of Pathology & Immunology; Director, Bursky Center for Human Immunology & Immunotherapy Programs; Washington University School of Medicine and a scientific founder of Asher Bio, reviewed new preclinical data from studies of CD8-IL2, a murine surrogate of AB248, which was evaluated in a T3 sarcoma model. The data showed that:

In an anti-PD-1 resistant tumor model, a single dose of CD8-IL2 resulted in complete tumor rejection in 90% of treated mice. In contrast, high dose IL-2 produced minimal efficacy.
Treatment with CD8-IL2 led to the expansion of antigen specific T cells with increased expression of activation-associated markers and reduced expression of exhaustion-associated markers.
CD8-IL2 monotherapy was well-tolerated, demonstrating therapeutic activity without inducing body weight loss.
In a poster titled, "Selective activation of CD8+ T cells by a CD8-targeted IL-2 results in enhanced anti-tumor efficacy and safety," lead author Kelly Moynihan, Ph.D., Associate Director and AB248 Program Lead at Asher Bio, described the design of ­cis-targeted CD8-IL2 molecules and reviewed preclinical in vitro and in vivo data, which showed that:

Treatment with a single dose of CD8-IL2 resulted in a majority of complete responses in established MC-38 tumors, and superior efficacy as compared to a "not α" IL-2. CD8-IL2 also showed marked synergy in combination with an anti-PD1 against established B16F10 melanomas, inducing complete responses in 100% of treated mice.
Efficacy with a "not α" IL-2 in mice cannot be achieved unless "not α" IL-2 is dosed to levels that drive a high degree of toxicity-induced body weight loss (>10%). In contrast, treatment with CD8-IL2 drives strong anti-tumor efficacy without inducing body weight loss.
Treatment with CD8-IL2 led to selective expansion of CD8+ T cells in both the peripheral blood and tumor compartments in mice, and in cynomolgus monkeys, showed strong and selective expansion of CD8+ T cells.
Both presentations will be available in the "Presentations and Posters" section of Asher Bio’s website: View Source

On November 12, 2021 Avenue Therapeutics, Inc. (or the "Company") (NASDAQ: ATXI), a company focused on the development of intravenous ("IV") tramadol for the U.S. market, reported the closing of its public offering of 1,946,787 shares of common stock at a public offering price of $1.34 (Press release, Avenue Therapeutics, NOV 12, 2021, View Source [SID1234595459]). The gross proceeds of the offering were approximately $2.6 million before deducting underwriting discounts, commissions and offering expenses. In addition, the Company has granted Aegis Capital Corp. a 45-day option to purchase up to an additional 292,018 shares of common stock to cover over-allotments, if any, at the public offering price, less the underwriting discount.

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The common stock is trading on The Nasdaq Capital Market under the symbol "ATXI".

Aegis Capital Corp. acted as the sole book-running manager for the offering.

A registration statement on Form S-3 relating to common stock being sold in this offering was declared effective by the Securities and Exchange Commission (the "SEC") on October 1, 2021. The offering was made only by means of a prospectus. Copies of the final prospectus may be obtained on the SEC’s website, www.sec.gov, or by contacting Aegis Capital Corp., Attention: Syndicate Department, 810 7th Avenue, 18th Floor, New York, NY 10019, by email at [email protected], or by telephone at (212) 813-1010.

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 jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On November 12, 2021 Actinium Pharmaceuticals, Inc. (NYSE AMERICAN: ATNM) ("Actinium" or the "Company"), a leader in the development of targeted radiotherapies for patients with unmet needs, reported that data highlighting an anti-HER2 antibody radiation conjugate (ARC) in combination with a CD47 blocking antibody immunotherapy in solid tumor models are being presented at the 36th Annual Meeting of the Society for Immunotherapy for Cancer (SITC 2021) November 12th – 14th (Press release, Actinium Pharmaceuticals, NOV 12, 2021, View Source [SID1234595458]). Actinium evaluated the anti-HER2 antibody trastuzumab (Herceptin) conjugated with either Actinium-225 (Ac-225) or Lutetium-177 (Lu-177) radioisotope payloads to explore potential synergies in combination with CD47 blocking antibodies. CD47 is a macrophage checkpoint which is upregulated in certain cancers, that acts as a "don’t eat me" signal on cancer cells to suppress phagocytosis and evade detection and destruction by the immune system. Actinium is exploring ARC combinations with CD47 blocking antibodies in solid tumors and blood cancers to evaluate mechanistic synergies including the ability to upregulate the cell surface "eat me" signal calreticulin via targeted radiotherapy.

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(PRNewsfoto/Actinium Pharmaceuticals, Inc.)

HER2-ARC + anti-CD47 SITC (Free SITC Whitepaper) Poster Highlights

HER2 targeting properties remained intact after radiolabeling trastuzumab with Ac-225 or Lu-177 as determined by binding to HER2 expressing cells
Calreticulin cell surface levels were increased in multiple cell lines after exposure to HER2-ARC
Phagocytosis was increased as much as 2-fold with the combination of a HER2-ARC and an anti-CD47 antibody compared to either as a single agent
Enhanced therapeutic efficacy with both improved tumor control and survival with the HER2-ARC and anti-CD47 blocking antibody combination compared to either as a single agent shown solid tumors in vivo models
Dr. Helen Kotanides, Vice President, Translational Research and Preclinical Development, stated, "We’re excited to present the first combination data from a CD47 targeting agent with an ARC in solid tumors. CD47 blocking agents hold tremendous potential but have yet to produce meaningful responses in solid tumors as monotherapies. Given our expertise in the area of targeted radiotherapy, we strongly believe that an ARC could synergize with CD47 blocking therapies given their immunogenic and cytotoxic properties. Specifically, we hypothesized that targeted radiotherapy could upregulate calreticulin, an "eat me" signal, to enhance phagocytosis and anti-tumor activity when combined with a CD47 blocking therapy. These results being presented at SITC (Free SITC Whitepaper) are highly encouraging and support not only our hypothesis of mechanistic synergy but also the continued development of this combination in HER2-positive and other solid tumor indications."

Sandesh Seth, Actinium’s Chairman and CEO, said, "We are excited to present this data at SITC (Free SITC Whitepaper) as it emanates from our renewed R&D focus on creating value by demonstrating the power of combining ARCs with immunotherapy for a better clinical effect by leveraging our platform capabilities. These data will support our pipeline expansion into solid tumors and combinations with immunotherapy. With the field of CD47 targeting agents growing rapidly, there is increasing competition not only in blood cancer indications but also in solid tumors, resulting in a need for differentiation. This data will also allow us to explore collaborations and partnerships with companies developing CD47 targeting agents with the goal of improving patient outcomes via the mechanistic synergy and highly differentiated profile of ARCs."

SITC Poster Details

Poster Title: Enhancement of the anti-tumor effects of CD47 blockade in solid tumors by combination with targeted radioimmunotherapy

Poster Number: 589

Location: Poster Hall, Walter E. Washington Convention Center in Washington, D.C.

Dates and Times: 11/12/2021 – 11/14/2021, 7:00 am – 5:00 pm

The poster will be accessible on Actinium’s website on the Presentations & Webinars page: View Source

On November 12, 2021 Savara Inc. (Nasdaq: SVRA), a clinical stage biopharmaceutical company focused on rare respiratory diseases, reported financial results for the third quarter ending September 30, 2021 and provided a business update (Press release, Savara, NOV 12, 2021, View Source [SID1234595457]).

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"The team is focused and driving hard on advancing the pivotal Phase 3 IMPALA 2 trial," said Matt Pauls, Chair and Chief Executive Officer, Savara. "Given that an increasing number of sites are actively screening and enrolling patients, and we completed an important regulatory milestone with EMA’s acceptance of our proposed revised PIP, we are pleased with our progress over the last quarter. While the potential impact of COVID-19 and the flu over the winter is unknown, we remain confident in our guidance of a 20-month enrollment timeframe and top-line data by the end of Q2 2024. Finally, we significantly bolstered our inhalation delivery and biological product expertise in the manufacturing, regulatory, and quality functions with the addition of Peter Clarke and Charles LaPree."

Third Quarter Financial Results (Unaudited)
Savara’s net loss attributable to common stockholders for the three months ended September 30, 2021, was $10.5 million, or $(0.07) per share, compared with a net loss attributable to common stockholders of $11.1 million, or $(0.18) per share, for the three months ended September 30, 2020.

Research and development expenses increased by $0.9 million, or 16.6%, to $6.5 million for the three months ended September 30, 2021 from $5.6 million for the three months ended September 30, 2020. The increase was primarily attributable to an approximately $3.2 million increase in costs associated with the screening of patients and progression of the IMPALA-2 trial for the molgramostim development program. This was partially offset by a $2.1 million decrease in chemistry, manufacturing, and control ("CMC") and clinical operations activities associated with the wind down of the vancomycin study in methicillin-resistant Staphylococcus aureus (MRSA) lung infection.

General and administrative expenses decreased by $2.0 million, or 36.7%, to $3.4 million for the three months ended September 30, 2021 from $5.4 million for the three months ended September 30, 2020. The decrease was primarily due to the recognition of a one-time non-recurring charge of $0.8 million for non-cash stock-based compensation and approximately $1.5 million of paid and accrued severance payments to former members of executive management during the three months ended September 30, 2020.

As of September 30, 2021, Savara had cash, cash equivalents, and short-term investments of approximately $171 million and debt of approximately $25 million.

On November 12, 2021 Aptevo Therapeutics Inc. ("Aptevo" or the "Company") (NASDAQ:APVO), a clinical-stage biotechnology company focused on developing novel immuno-oncology therapeutics based on its proprietary ADAPTIR and ADAPTIR-FLEX platform technologies, reported its financial results and business highlights for the quarter ended September 30, 2021 (Press release, Aptevo Therapeutics, NOV 12, 2021, View Source [SID1234595456]).

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Business Highlights

Enrollment and dosing have commenced in Part 2 (Expansion Phase) of Company’s multicenter 5001 Phase 1B clinical trial to evaluate APVO436 in adult patients with acute myeloid leukemia (AML).
Reported 3 publications in two peer-reviewed journals ( Cancers[Basel]) and Frontiers in Aging) regarding the salient features of the data obtained during Part 1 (Dose escalation phase) of the 5001 APVO436 Phase 1B trial.
Participated in Euroleukemia2021 Meeting with an oral and a poster presentation.
Showcased the Company’s preclinical assets, APVO442 and APVO603, and their potential to improve efficacy in the treatment of solid tumors and participated in discussions about risk mitigation in cell engager candidates at the Virtual Cell Engager Summit.
Presented the unique aspects of the Company’s proprietary ADAPTIR AND ADAPTIR-FLEX platforms at the Cambridge Health Institute PEGS Virtual Conference.
platforms at the Cambridge Health Institute PEGS Virtual Conference.
"I am excited about our clinical progress in the third quarter, as we initiated enrollment and dosing in our APVO436 Phase 1b expansion trial. We look forward to receiving data from this trial in the first half of next year and will use the outcomes to inform our go-forward clinical strategy for this promising lead clinical candidate with the potential to impact existing standard of care for acute myeloid leukemia," said Marvin White, President and CEO of Aptevo. "During the quarter we were fortunate to present our clinical work in two peer-reviewed journals and to showcase our ADAPTIR and ADAPTIR-FLEX platforms at multiple industry conferences. We are well funded to continue our work for the next twelve months and look forward to reporting our progress."

Third Quarter 2021 Financial Results Summary

Cash Position : Aptevo had cash and cash equivalents as of September 30, 2021 totaling $53.4 million, including restricted cash of $1.3 million. The restricted cash is expected to be released over the next twelve months.

Royalty Revenue: Royalty revenue was $3.1 million for the three months ended September 30, 2021, related to the royalty from Pfizer on global net sales of RUXIENCE , a biosimilar to the drug RITUXAN , launched by Pfizer in early 2020. RUXIENCE is a trademark of Pfizer; RITUXAN is a trademark of Biogen. Due to our continuing involvement under the Definitive Agreement originally between Trubion and Wyeth, we continue to recognize royalty revenue on net sales of RUXIENCE and record the royalty payments to HCR as a reduction of the liability when paid. As such payments are made to HCR, the balance of the liability will be effectively repaid over the life of the Royalty Purchase Agreement.

Research and Development Expenses : Research and development expenses decreased to $4.4 million for the three months ended September 30, 2021 from $4.5 million for the three months ended September 30, 2020. Costs associated with APVO436 clinical trial increased as we continued to advance that trial and have now started dosing in our Phase 1b Expansion program. This increase was offset by lower spending on preclinical projects.

General and Administrative Expenses : For the three months ended September 30, 2021, general and administrative expenses increased to $3.5 million from $3.2 million for September 30, 2020, with higher costs related to responding to stockholder activism matters and higher employee costs.

Other Expense, Net: Other expense, net consists primarily of costs related to debt extinguishment, accrued exit fees on debt, non-cash interest on financing agreements, and interest on debt. Other expense, net was $2.3 million for the three months ended September 30, 2021 and $0.7 million for the three months ended September 30, 2020. The increase in other expense, net is primarily related to interest expense and accrued exit fees for the MidCap Credit Agreement, as well as non-cash interest expense for the HCR Purchase Agreement.

Discontinued Operations: Income from discontinued operations was approximately $0.1 million for the three months ended September 30, 2021 and September 30, 2020, related to collection of deferred payments from Medexus earned on second quarter 2021 and 2020 IXINITY sales.

Net Loss : Aptevo’s net loss for the three-month period ended September 30, 2021 was $7.0 million or $1.43 per share, as compared to a net loss of $6.8 million or $2.10 per share for the corresponding period in 2020.

Liability Related to Sale of Future Royalties: We treat the Royalty Purchase Agreement with HCR as a debt financing, amortized under the effective interest rate method over the estimated life of the related expected royalty stream. The liabilities related to sale of future royalties and the debt amortization are based on our current estimates of future royalties expected to be paid over the life of the arrangement. We will periodically assess the expected royalty payments using projections from external sources. To the extent our estimates of future royalty payments are greater or less than previous estimates or the estimated timing of such payments is materially different than previous estimates, we will adjust the effective interest rate and recognize related non-cash interest expense on a prospective basis. We are not obligated to repay the proceeds received under the Royalty Purchase Agreement with HCR.