Synthetic Biologics Announces Planned Transformative Acquisition of VCN Biosciences; Developer of a Novel Oncolytic Virus Platform Targeting Pancreatic and other Solid Tumors

On December 14, 2021 Synthetic Biologics, Inc. (NYSE American: SYN), a diversified clinical-stage company developing therapeutics designed to treat diseases in areas of high unmet need, reported it has signed a definitive agreement to acquire VCN Biosciences, S.L. (VCN), which is developing a new oncolytic adenovirus (OV) platform designed for intravenous (IV) delivery to trigger tumor cell death and promote immune cell infiltration into tumors (Press release, Synthetic Biologics, DEC 14, 2021, View Source [SID1234597103]). Total upfront consideration for the acquisition is $4.7 million in cash plus the assumption of $2.4 million of VCN liabilities. Additionally, VCN will receive shares of Synthetic Biologics’ common stock representing 19.99% of the total shares outstanding of the Company’s common stock. The Company has also agreed to an additional $70.3 million of payments contingent upon the achievement of future milestones, a majority of which are tied to late-stage clinical development and regulatory achievements. The transaction is expected to close during the first quarter of 2022, and is subject to, among other things, the approval by the Spanish government of the Company’s acquisition of VCN under Spain’s Foreign Investment Act and other customary closing conditions. Additional details regarding the transaction are available in the Company’s Current Report on Form 8-K, which has been filed with the Securities and Exchange Commission and is available on the Company’s website.

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Synthetic Biologics, Inc. www.syntheticbiologics.com (PRNewsFoto/Synthetic Biologics, Inc.)

VCN’s technology platform is designed to overcome critical challenges that restrict the development of the majority of OV therapies today. Unlike many OVs that can only be administered by direct intratumoral injection, VCN’s OVs are designed for systemic intravenous administration to target primary as well as metastatic tumors. Once inside the tumor, VCN’s OVs are designed to replicate selectively and aggressively, and to produce hyaluronidase (PH20), an enzyme that digests hyaluronan, a key component of the dense tumor stroma that often plays a crucial role in tumor progression. Degradation of tumor stroma has been shown to diminish a significant physical and immunosuppressive barrier to cancer treatment and thereby improve access to the tumor by additional therapies such as chemo and immuno-therapies. Results from previously completed clinical trials demonstrate that this process can occur for weeks or months following a single intravenous injection with a VCN OV. VCN is seeking to leverage these unique capabilities to address cancers with a high unmet need.

VCN OVs are also designed to be administered intratumorally or intravitreally (in the eye), either as a monotherapy or in combination with standard of care, to treat a wide variety of cancer indications. Combination treatment of VCN OVs with a variety of chemotherapies and immunotherapies such as checkpoint inhibitors and CAR-T cells are in early clinical testing or planned. VCN has the rights to four exclusive patents for proprietary technologies, as well as technologies developed in collaboration with the Virotherapy Group of the Catalan Institute of Oncology (ICO-IDIBELL), with a number of additional patents pending.

VCN’s lead drug candidate, VCN-01, has been evaluated in four Phase 1 clinical trials to date, including in patients with pancreatic cancer, head and neck squamous cell carcinoma, and retinoblastoma (Rb). In a Phase 1 clinical trial, patients with metastatic pancreatic ductal adenocarcinoma (PDAC) received the combination therapy of intravenous VCN-01 with the standard of care chemotherapy Gemcitabine plus Abraxane (G/A). Best results were observed when VCN-01 was administered one week before the first G/A dose. VCN-01 was well tolerated and when combined with G/A demonstrated an improved median overall and progression free survival, as well as a high response rate compared to G/A alone. These data compare favorably with current standard of care and are the basis of a planned Phase 2 clinical trial of the higher dosing level.

VCN-01 is also being studied as a monotherapy in patients with retinoblastoma (RB) who previously failed chemotherapy. Intravitreal administration of VCN-01 produced a complete remission and a reduction of tumors in several patients. These promising outcomes form the basis for an Orphan Drug application with the FDA and are planned to be explored in a larger future clinical trial.

VCN is also developing a next generation Albumin Shield technology platform, VCN-11, which builds upon the pre-clinical and clinical results of VCN-01. VCN-11 incorporates an albumin binding domain in the virus outer shell designed to enable the virus to coat itself with host serum albumin, potentially preventing its inactivation by neutralizing antibodies in the bloodstream en route to the tumor. The addition of the Albumin Shield technology is not expected to interfere with VCN-11’s ability to target tumor cells and may allow for repeated administration to optimize tumor exposure.

Steven A. Shallcross, Chief Executive Officer of Synthetic Biologics, commented, "We are excited to announce this transformative acquisition, as VCN’s platform represents a potentially breakthrough approach to cancer treatment with oncolytic viruses by allowing for systemic delivery, high selectivity and enhanced tumor access. In addition to triggering tumor cell death, these therapies have been shown to elicit a strong anti-tumor immune response. The results of the Phase 1 clinical trial in PDAC, a highly aggressive and lethal malignancy, are very encouraging with respect to tumor response and survival. Significantly, biopsies in these patients confirmed up regulation of tumor immune markers and induction of a robust antitumor immune response, including increased tumor infiltration by cytotoxic T-cells. These results suggest VCN-01 holds significant potential to increase the addressable market for checkpoint inhibitors and CAR-T therapies, as these therapies have historically been less effective immunologically against "cold" tumors like PDAC."

"Based on encouraging results of prior preclinical and clinical trials of VCN-01, we plan to initiate a controlled Phase 2 clinical trial of VCN-01 at multiple centers across the US and EU. There is a significant unmet need for a safe and effective therapy for patients with pancreatic cancer, a condition in which most people diagnosed do not survive more than a year following their initial diagnosis. Based on highly encouraging early clinical results, we also plan to conduct a registrational trial in pediatric patients with advanced Rb. Importantly, this is an underserved patient population and we believe VCN-01 holds tremendous promise to preserve the eyes of these patients, who are typically less than two years old at diagnosis. We believe these trials can be conducted relatively quickly and efficiently. At the same time, we are also evaluating investigator-sponsored studies combining VCN-01 with CAR-T therapies, as well as VCN-01 in other orphan indications such as glioblastoma. We look forward to providing additional details on the timing and design of these trials in the near future."

"VCN was founded by internationally recognized experts in oncolytic adenoviruses for cancer treatment and I will be delighted to welcome them to our team. VCN’s novel therapies allow for a robust and efficient manufacturing process, with an attractive cost structure. The platform is supported by a growing intellectual property (IP) portfolio that provides it patent protection through at least 2030 with additional patents underway that we believe would further strengthen our IP portfolio. Importantly, VCN-01 has been granted Orphan Drug Designation by the European Medicines Agency (EMA), which may provide a number of benefits including up to ten years of market exclusivity. Importantly, we have a strong balance sheet with over $72.1 million of cash as of September 30, 2021, which we believe will provide us significant runway to both support our existing programs, as well as to able to advance VCN-01 and VCN-011 through important milestones that we believe will drive significant shareholder value."

Manel Cascalló, PhD, Chief Executive Officer of VCN, noted, "Joining together with Synthetic Biologics is a significant opportunity as it allows us to partner with an experienced team, well-versed in drug development, manufacturing, and commercialization. We anticipate the combined company will have the financial resources to fund our clinical programs to key value inflection points and we look forward to a successful future together."

Conference Call

Synthetic Biologics will hold a conference call today, December 14, 2021, at 10:00 a.m. Eastern Time. The dial-in information for the call is as follows, U.S. toll free: 1-888-347-5280 or International: +1 412-902-4280. Participants are asked to dial in 15 minutes before the start of the call to register. The call will also be webcast over the Internet at View Source." target="_blank" title="View Source." rel="nofollow">View Source An archive of the call will be available for replay at the same URL, View Source, for 90 days after the call.

Molecular Partners Announces Collaboration with Novartis to Develop DARPin-Conjugated Radioligand Therapeutic Candidates for Oncology

On December 14, 2021 Molecular Partners AG (SIX: MOLN; NASDAQ: MOLN), a clinical-stage biotech company developing a new class of custom-built protein drugs known as DARPin therapeutics, reported a collaboration with Novartis in the form of a license agreement to develop, manufacture and commercialize DARPin-conjugated radioligand therapies (DARPin-RLTs) (Press release, Molecular Partners, DEC 14, 2021, View Source [SID1234597100]). The collaboration will combine Molecular Partners’ industry-leading ability to rapidly generate high-affinity DARPins and the RLT capabilities and expertise of Novartis.

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By harnessing the power of radioactive atoms and applying it to cancers through targeted radioligand therapy, RLTs have the potential to deliver molecularly targeted radiation to tumor cells anywhere in the body. Under the terms of the agreement, Molecular Partners will collaborate with Novartis to discover DARPin-RLTs that target specific tumor associated antigens. DARPins have great potential to enable robust, tumor-specific delivery of radioligands owing to their small size, allowing for greater tumor penetration, and high specificity and affinity.

"We are very pleased to announce this new collaboration with Novartis. For several years, the team at NIBR has established themselves as the world leader in the RLT field and working with them on this program is an easy choice to make," said Patrick Amstutz, CEO of Molecular Partners. "While DARPins can be designed to perform any number of biological tasks, here we highlight some of their innate characteristics, including small size and high specificity and affinity, which may offer an advantage to RLT’s which often require a highly specific delivery vehicle."

"Radioligand therapy is a transformative platform for delivering radiation to target cells, and DARPins are a unique modality for specifically targeting tumors," said Jay Bradner, President of the Novartis Institutes for BioMedical Research. "The marriage of these two technologies is designed to enable us to target radioligands directly to tumor cells anywhere in the body with the goal of improving and extending patients’ lives."

Under the agreement, both parties will collaborate on the discovery and optimization of the therapeutic candidates. Novartis would be responsible for all clinical development and commercialization activities. Novartis will pay $20 million upfront to Molecular Partners, total potential development, regulatory and commercialization milestone payments of up to $560 million, and up to low double-digit percent of royalties.

Infinity Pharmaceuticals Added to the NASDAQ Biotechnology Index

On December 14, 2021 Infinity Pharmaceuticals, Inc. (NASDAQ: INFI) a clinical-stage biotechnology company developing eganelisib, a potentially first-in-class, oral, immuno-oncology macrophage reprogramming therapeutic, reported it has been selected for addition to the NASDAQ Biotechnology Index (NASDAQ: NBI), effective as of market open on Monday, December 20, 2021 (Press release, Infinity Pharmaceuticals, DEC 14, 2021, View Source [SID1234597089]).

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The NBI is designed to track the performance of a set of securities listed on the NASDAQ Stock Market (NASDAQ), made up of NASDAQ-listed companies classified as Biotechnology & Pharmaceuticals by the Industry Classification Benchmark (ICB), and is widely used by investment managers and institutional investors for index funds and as benchmarks for active investment strategies. To be selected for addition to the NBI, a company must have a minimum market capitalization of $200 million; demonstrate an average daily trading volume of at least 100,000 shares; and must be Nasdaq-listed. The index is modified market capitalization-weighted such that constituents are capped at 8% (for the top 5) and at 4% (for the remaining) at each quarterly index rebalance; the entire index is reviewed and reconstituted annually in December.

"We are very gratified that Infinity’s progress has been recognized by the addition of INFI to the prestigious Nasdaq Biotechnology Index," said Adelene Perkins, Chief Executive Officer and Chair, Infinity Pharmaceuticals. "Our eganelisib data have continued to mature in very positive ways with presentations at SABCS and ASCO (Free ASCO Whitepaper) GU this year, demonstrating clinically meaningful outcomes in both metastatic triple negative breast cancer and urothelial cancer, respectively. Being included in this index is another important milestone as we continue to pursue bringing significantly better treatments to cancer patients."

For more information about the NASDAQ Biotechnology Index visit www.nasdaq.com.

TG Therapeutics Announces Data from the UNITY-CLL Phase 3 Trial Presented at the 63rd American Society of Hematology (ASH) Annual Meeting

On December 14, 2021 TG Therapeutics, Inc. (NASDAQ: TGTX), reported two data presentations, highlighted data from the UNITY-CLL Phase 3 trial evaluating the combination of ublituximab, the Company’s investigational anti-CD20 monoclonal antibody and UKONIQ (umbralisib), the Company’s inhibitor of PI3K-delta and CK1-epsilon, (U2), in patients with both treatment naïve and relapsed or refractory chronic lymphocytic leukemia (CLL) (Press release, TG Therapeutics, DEC 14, 2021, View Source [SID1234597087]). Data presentations occurred yesterday evening during the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting and exposition. Presentation highlights are included below.

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Michael S. Weiss, Chairman and Chief Executive Officer of TG Therapeutics stated, "We are pleased to share two presentations last night at the ASH (Free ASH Whitepaper) annual meeting which included additional analyses of the UNITY-CLL Phase 3 trial evaluating the U2 combination in patients with both treatment naïve and relapsed or refractory CLL. We believe these presentations showcase the versatility of the U2 combination both by treatment subgroup, and also interestingly in a patient population generally characterized as unsuitable for BTKi-based therapy. While significant advances have been made in the treatment of CLL, there still remains underserved patients who may not be good candidates for or fail to respond to currently available treatments."

PRESENTATION HIGHLIGHTS

Poster Presentation Title: Efficacy and Safety of Ublituximab in Combination with Umbralisib (U2) in Patients with Chronic Lymphocytic Leukemia (CLL) By Treatment Status: A Sub-Analysis of the Phase 3 Unity-CLL Study

A total of 210 CLL patients were enrolled in the U2 cohort of the UNITY-CLL trial, including 119 treatment naïve and 91 previously treated.
Efficacy and safety highlights for the treatment naïve (TN) population included:
Independent review committee (IRC) assessed progression-free survival (PFS) of U2 in the TN population was 38.5 months, with two-year PFS of 76.6%
84% IRC-assessed overall response rate (ORR) in the TN population, including 5% complete response (CR)/complete response with incomplete marrow recovery (CRi)
Responses were durable with 76% maintaining response at 2 years
Grade 3/4 adverse events (AEs) of special interest occurring in the TN population included ALT elevation (12%), AST elevation (8%), rash (3%), pneumonia (7%), non-infectious colitis (3%), pneumonitis (1%) and opportunistic infections (1%).
Efficacy and safety highlights for the previously treated population (PT) included:
IRC-assessed PFS in the PT population was 19.5 months, with two-year PFS of 41.3%
82% IRC-assessed ORR in the PT population, including 4% CR/CRi
Responses were durable, with 43% maintaining response at 2 years
Grade 3/4 adverse events (AEs) of special interest occurring in the PT population included ALT elevation (3%), AST elevation (2%), rash (1%), pneumonia (11%) and opportunistic infections (1%).
Poster Presentation Title: Favorable Outcomes for Patients Treated with U2 with Co-Morbidities or Concomitant Medications: A Retrospective Analysis of Unity-CLL Phase 3 Trial

A total of 210 CLL patients were enrolled in the U2 cohort of the UNITY-CLL trial, including 119 treatment naïve and 91 previously treated.
131 (64%) of U2 treated patients had at least 1 comorbid condition or concomitant medication (conmed) that could pose potential issues with BTKi therapy.
88% ORR, including 5% CR, for those patients with at least 1 comorbidity or conmed (n=131), compared to 83% ORR, including 5% CR, for the entire U2 population (n=210).
No difference in IRC-assessed PFS was observed between the group of patients with at least 1 comorbidity or conmed compared to the entire U2 population (31.9 months for both groups).
Grade 3/4s AEs of clinical interest in the group of patients with at least 1 comorbidity or conmed and the entire U2 population respectively, included ALT elevation (8%, 8%), AST elevation (4%, 5%), non-infectious colitis (3%, 2%) and pneumonitis (1%, 0.5%).
The above referenced presentations are now available on the Publications page of the Company’s corporate website at View Source

Galera Announces Primary Endpoint Met Statistical Significance in Corrected Topline Efficacy Data of Phase 3 ROMAN Trial of Avasopasem

On December 14, 2021 Galera Therapeutics, Inc. (Nasdaq: GRTX), a clinical-stage biopharmaceutical company focused on developing and commercializing a pipeline of novel, proprietary therapeutics that have the potential to transform radiotherapy (RT) in cancer, reported that corrected results from its Phase 3 ROMAN trial of avasopasem for the treatment of RT-induced severe oral mucositis (SOM) in patients with locally advanced head and neck cancer (HNC) achieved statistical significance on the primary endpoint of reduction in the incidence of SOM. Avasopasem has been granted Breakthrough Therapy Designation (BTD) by the U.S. Food and Drug Administration (FDA) for the reduction of SOM induced by RT (Press release, Galera Therapeutics, DEC 14, 2021, View Source [SID1234597086]).

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The Company previously announced the Phase 3 ROMAN trial of avasopasem in SOM did not achieve statistical significance on the primary endpoint. Upon further analysis, an error by the contract research organization (CRO) was identified in the statistical program. Correction of this error resulted in improved p-values for the primary and secondary endpoints.

The corrected p-values are as follows:

16% relative reduction in the incidence of SOM in the avasopasem treatment group (54%) vs. placebo group (64%) (p=0.0451*) (previously reported as p=0.113) (primary endpoint)
56% relative reduction in the number of days of SOM in the avasopasem treatment group (8 days) vs. placebo group (18 days) (p=0.0022*) (previously reported as p=0.011) (secondary endpoint)
27% relative reduction in the severity (incidence of Grade 4 OM) of SOM in the avasopasem treatment group (24%) vs. placebo group (33%) (p=0.052) (previously reported as p=0.167) (secondary endpoint)
The Company also announced topline results from its single-arm Phase 2a EUSOM trial of avasopasem in Europe for RT-induced SOM in patients with HNC undergoing standard-of-care RT + cisplatin. This trial was conducted in 12 centers across six countries in Europe and enrolled 38 patients, of which 33 completed full treatment. Avasopasem appeared to be generally well tolerated. In EUSOM, the incidence of SOM was 54.5% and the median number of days of SOM was 9 days, in line with the ROMAN trial in which the incidence was 54% and the median duration was 8 days.

"Given the high unmet medical need for patients with head and neck cancer who develop radiotherapy-induced severe oral mucositis, we are gratified that the Phase 3 ROMAN trial achieved statistical significance on the primary endpoint after the correction of the statistical programming error," said Mel Sorensen, M.D., President and CEO of Galera. "ROMAN is our second randomized trial conducted in patients with head and neck cancer to achieve statistical significance and demonstrate improved clinical benefit. As we continue to analyze the full data set and evaluate our resources, we look forward to meeting with the FDA in 2022 to discuss whether the results from this single Phase 3 trial together with the randomized Phase 2b trial could support an NDA submission."

Approximately 42,000 HNC patients undergo standard-of-care RT every year in the U.S. and are at risk of experiencing SOM, painful mouth sores that impact the ability to eat and drink. In market research, both radiation oncologists and patients cite SOM as the most burdensome RT toxicity in HNC treatment. Currently, there are no FDA approved drugs to reduce the incidence or duration of SOM in solid tumors.

Continued Dr. Sorensen, "In parallel, our anti-cancer therapeutic trials in lung and pancreatic cancer, which we refer to as the GRECO-1 and GRECO-2 trials, respectively, are currently enrolling, and we look forward to reporting initial data from our GRECO-1 trial in the first half of 2022. Both trials combine our second dismutase mimetic candidate, rucosopasem, with stereotactic body radiation therapy (SBRT) with the goal of augmenting the anti-cancer efficacy of SBRT."

Conference Call

Galera will host a conference call and live audio webcast on Tuesday, December 14 at 8:30 a.m. ET to discuss the ROMAN Phase 3 data, including additional analyses from the full data set, and provide a general business update. The webcast will be accessible from the Investors page of Galera’s website, investors.galeratx.com, and an archived version of the webcast will be available in the News & Events section of the Investors page of Galera’s website for 30 days following the event.