On December 14, 2020 Avelas Biosciences, Inc., pioneering the field of intraoperative fluorescent cancer imaging, reported that the company has received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) for pegloprastide (AVB-620) for the intraoperative detection and visualization of positive margins during breast cancer surgery (Press release, Avelas Biosciences, DEC 14, 2020, View Source [SID1234572803]). Pegloprastide is designed to deliver a fluorescent marker to cancer cells to aid surgeons in identifying positive margins in real time during surgery. Positive margins can be a sign that cancer may be left behind, requiring a second surgery.

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"We now have clarity on the development path to make fluorescence image-guided surgery the new standard of care for breast cancer lumpectomies," said Jay Lichter, Ph.D., Chairman, President, and Chief Executive Officer of Avelas. "Pegloprastide has the potential to greatly reduce the number of repeat surgeries, potentially improving outcomes for hundreds of thousands of women and saving thousands of lives."

The presence of positive margins is a significant challenge in breast-conserving surgery. Positive surgical margins occur when post-operative pathology indicates cancer cells are present at or very close to the edge of removed tissue, indicating that there may be residual cancer left behind after an operation. It is estimated that each year in the United States more than 260,000 women undergo a lumpectomy, of which one-third (more than 80,000) are repeat surgeries with the goal of achieving negative margins.1 Beyond that, of the estimated 90,000 women who choose a mastectomy, many choose it for fear of incomplete initial lumpectomy or due to an initial attempt at a lumpectomy that resulted in positive margins.1

The FDA’s Breakthrough Therapy designation is intended to expedite the development and review of a drug candidate that is under investigation to treat a serious or life-threatening disease or condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints. A Breakthrough Therapy designation provides more intensive FDA guidance on an efficient drug development program, an organizational commitment involving senior managers, and eligibility for rolling review and priority review.

Previously reported positive top-line data from the company’s completed Phase 2/3 study, which evaluated the safety and efficacy of pegloprastide in women with primary, nonrecurrent breast cancer undergoing surgery, met its primary endpoint of detecting cancer in margin specimens in real time (p<0.001). The data showed use of pegloprastide during surgery correctly identified cancer in up to 75% of patients who would have otherwise been candidates for a repeat (re-excision) surgery. Observed re-excision rate in the study was 6% in patients whose surgeries included pegloprastide. Current re-excision rates are estimated at 20-40% among all patients receiving an initial lumpectomy. 2-7

About Pegloprastide (AVB-620) and QUEST SPECTRUM Fluorescent Imaging Device

Pegloprastide (AVB-620) is based on the science of activatable cell-penetrating peptides and is the only fluorescence-based clinical cancer detection product that uses the ratio of two fluorophores within the same molecule (ratiometric imaging) to provide more accurate and actionable information. Pegloprastide’s ratiometric readout attenuates common artifacts of fluorescent imaging, including differences in drug concentration and distance of the camera from the tissue area of interest. Pegloprastide is used during surgery with a specialized fluorescent imaging device manufactured for Avelas by Quest Medical Imaging, based on its QUEST SPECTRUM platformtechnology. QUEST SPECTRUM device has a wide field of view and provides a rapid assessment of tissue. Beyond breast cancer, Avelas has plans to explore the use of pegloprastide during surgery for other types of cancer, including ovarian, colorectal, head and neck, melanoma, and sarcoma.

About Quest

Quest Photonic Devices is a group of companies that is developing high-end multispectral imaging cameras and light sources for medical and industrial use. Through its subsidiary companies, Quest Medical Imaging B.V. and Quest Medical Imaging Inc., Quest focuses specifically on the medical market of fluorescence image-guided surgery and is committed to improving patient care and surgical outcomes.

On December 14, 2020 RedHill Biopharma Ltd. (Nasdaq: RDHL) ("RedHill" or the "Company"), a specialty biopharmaceutical company, reported that the company was selected for addition to the NASDAQ Biotechnology Index (NASDAQ: NBI) (Press release, RedHill Biopharma, DEC 14, 2020, View Source [SID1234572802]). The addition to the NBI will become effective prior to market open on Monday, December 21, 2020.

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The Index is used to designate a set of NASDAQ-listed securities to be acquired as part of index-defined funds to be used in investment portfolios. The biotechnology index is classified according to the Industry Classification Benchmark (ICB). Companies in the biotechnology index must meet eligibility requirements, including minimum market capitalization, average daily trading volume, seasoning as a public company, and other criteria. The index is evaluated annually and serves as the basis for the iShares NASDAQ Biotechnology Index Fund.

For more information about the NASDAQ Biotechnology Index, including eligibility criteria, visit View Source

On December 14, 2020 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of innovative therapeutics for the treatment of cancer, reported the closing of its underwritten public offering of 29,500,000 shares of its common stock, including the exercise in full by the underwriters of their option to purchase up to an additional 3,847,826 shares, at the public offering price of $5.75 per share (the Offering) (Press release, Curis, DEC 14, 2020, View Source [SID1234572801]). Curis expects the net proceeds from the Offering to be approximately $159.1 million, after deducting underwriting discounts and commissions and estimated offering expenses.

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Cantor Fitzgerald & Co. and JonesTrading Institutional Services LLC acted as joint book-runners for the Offering. H.C. Wainwright & Co., LLC and Laidlaw & Company (UK) Ltd. acted as co-lead managers.

Curis intends to use the net proceeds from the Offering, together with its existing cash and cash equivalents, to continue development of CA-4948, in collaboration with Aurigene, and CI-8893, in collaboration with ImmuNext, and for general working capital and capital expenditures. Curis estimates that the net proceeds from the Offering, together with its existing cash and cash equivalents, will enable it to fund its operating expenses and capital expenditure requirements into 2023.

The securities in the Offering were offered pursuant to a shelf registration statement on Form S-3 (File No. 333-224627) that was filed with the United States Securities and Exchange Commission ("SEC") on May 3, 2018, and declared effective by the SEC on May 17, 2018 and an additional registration statement on Form S-3 (File No. 333-251211) filed pursuant to Rule 462(b) which became automatically effective on December 9, 2020. The offering was made only by a means of a written prospectus and a prospectus supplement that form a part of the registration statement. A final prospectus supplement and accompanying prospectus relating to the Offering has been filed with the SEC and is available on the SEC’s website at www.sec.gov. Copies of the final prospectus supplement and the accompanying prospectus may also be obtained by contacting Cantor Fitzgerald & Co., Attention: Capital Markets, 499 Park Ave., 6th Floor, New York, New York 10022 or by email at [email protected].

The securities described above have not been qualified under any state blue sky laws. This press release shall not constitute an offer to sell or the 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.

On December 14, 2020 Synlogic, Inc. (Nasdaq: SYBX), a clinical stage company bringing the transformative potential of synthetic biology to medicine, reported SYNB1891 has advanced into the combination therapy stage of the ongoing Phase 1 trial. SYNB1891 is an investigational drug for the intra-tumoral treatment of solid tumors and lymphoma, composed of an engineered Synthetic Biotic designed to activate the STING pathway in the tumor microenvironment in order to upregulate the patient’s immune response (Press release, Synlogic, DEC 14, 2020, View Source [SID1234572798]).

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SYNB1891 is being advanced due to acceptable safety at doses evaluated to date, intratumoral injection feasibility, successful escalation to clinically relevant dose levels, and evidence of target engagement and immune system upregulation.

"Our goal is to bring the benefits of immunotherapy to patients fighting cancer who do not have the option of immunotherapies today," said Aoife Brennan, M.B. Ch.B., Synlogic’s President and Chief Executive Officer. "Synlogic is designing Synthetic Biotic medicines that work uniquely inside the tumor microenvironment, boosting the patient’s immune response and promoting the body’s ability to detect and destroy cancer cells. The interim results of our monotherapy cohorts suggest SYNB1891 is working as designed, upregulating the immune system in the tumor microenvironment via the STING pathway. We are excited to move this study forward."

"The body of data validating our unique approach to immunomodulation with Synthetic Biotic medicines continues to grow," said Dr. Richard Riese, M.D., Synlogic’s Chief Medical Officer. "The investigation of SYNB1891 combined with the PD-L1 checkpoint inhibitor atezolizumab (Tecentriq) is warranted by the encouraging and consistent results we have seen thus far across preclinical models, tumor response, and biomarkers of target engagement. We would like to thank the investigators, patients, and their families who continue to work closely with us as we advance this novel therapy."

SYNB1891 Highlights

SYNB1891 is being evaluated in a Phase 1, open-label, multicenter study administered by intratumoral injection to patients with advanced, metastatic solid tumors or lymphomas (NCT04167137).
The monotherapy arm of the study has enrolled four dose cohorts to date. A maximum tolerated dose has not been reached. Enrollment of additional monotherapy dose escalation cohorts will continue.
Study results to date across four dose cohorts of SYNB1891 monotherapy demonstrate:
SYNB1891 is safe and well-tolerated at currently evaluated dose levels, as an intratumoral injection in a heterogenous patient population with no dose limiting toxicities or infections to date.
Treatment with SYNB1891 demonstrates activation of the STING pathway and target engagement as assessed by:
Upregulation of IFN-stimulated genes, chemokines, cytokines, and T-cell response
Pharmacodynamic effects including increases in serum cytokines
Evidence of durable stable disease was observed in two patients being treated for metastatic melanoma and metastatic small cell lung cancer. Both patients experienced disease progression on immunotherapy with anti- PD-1/PDL-1 antibodies prior to enrollment in the study.
The combination arm of the study will combine escalating dose levels of SYNB1891 with a fixed dose of the PD-L1 checkpoint inhibitor atezolizumab, to establish a recommended Phase 2 dose for the combination regimen.
The study protocol has been amended to allow for the injection of visceral lesions in addition to cutaneous and subcutaneous lesions in both monotherapy and combination therapy cohorts.
Results of the SYNB1891 Phase 1 study will be presented at a future medical meeting.
The clinical development plan for SYNB1891 is based on compelling research from preclinical studies that demonstrate anti-tumor activity and generation of immunological memory by SYNB1891 in mouse models of cancer, as well as its robust activation of human antigen presenting cells (APCs) that are key to the generation of an anti-tumoral immune response. The Nature Communications publication titled, "Immunotherapy with an engineered bacteria by targeting the STING pathway for anti-tumor immunity," details the engineering and characterization of SYNB1891 (Leventhal, D.S., Sokolovska, A., Li, N. et al. Nature Communications 11, 2739 (2020)).

Learn more about Synlogic’s programs and pipeline by visiting View Source

About SYNB1891
SYNB1891 is an investigational drug for the intra-tumoral treatment of solid tumors and lymphoma, composed of an engineered Synthetic Biotic strain of E. coli Nissle that produces cyclic di-AMP (CDA), a stimulator of the STING (STimulator of INterferon Genes) pathway. This mechanism can play a critical role in the initiation of an anti-tumor immune response via activation of APCs and presentation of tumor antigens. The bacterial chassis of SYNB1891 also stimulates the innate immune system by several other mechanisms, including via Toll-like receptors (TLRs), potentially adding to the magnitude of the overall immune response. While SYNB1891 has been engineered with safety features that are designed to prevent its replication unless supplemented with specific nutrients, the bacteria remain active for several days within the injected tumor to stimulate a local immune response. SYNB1891 is being evaluated in a Phase 1 clinical trial.

On December 14, 2020 Relay Therapeutics, Inc. (Nasdaq: RLAY), a clinical-stage precision medicine company transforming the drug discovery process by leveraging unparalleled insights into protein motion, reported it has entered into a worldwide license and collaboration agreement with Genentech, a member of the Roche Group, for the development and commercialization of RLY-1971, a potent inhibitor of SHP2 (Press release, Relay Therapeutics, DEC 14, 2020, View Source [SID1234572797]). Under the collaboration, Genentech will assume development of RLY-1971 with the potential to expand into multiple combination studies including with Genentech’s investigational inhibitor of KRAS G12C, GDC-6036.

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"RLY-1971 has the potential to serve as a backbone for combination therapy across numerous solid tumors and therefore represents an encouraging approach for cancer patients," said Sanjiv Patel, M.D., president and chief executive officer of Relay Therapeutics. "Roche and Genentech’s global footprint and deep expertise in oncology makes them the perfect partner for us to execute the broad development and commercialization of RLY-1971."

"Genentech has a longstanding commitment to understanding the underlying biology of KRAS, the most commonly mutated oncogene and an important driver of cancer growth," said James Sabry, M.D., Ph.D., global head of pharma partnering, Roche. "We are excited to partner with Relay Therapeutics, and we believe that the combination of KRAS G12C and SHP2 inhibitors together represents a promising approach that we hope could become a new treatment option for patients with KRAS G12C mutant tumors."

Under the terms of the agreement, Relay Therapeutics will receive $75 million in an upfront payment and is eligible to receive $25 million in additional near-term payments. Relay Therapeutics also has the right to opt in to a 50/50 U.S. profit/cost share on RLY-1971. If Relay elects to opt in, then Relay will be eligible to receive 50 percent of profits from U.S. sales and up to $410 million in additional ex-U.S. commercialization and sales-based milestone payments, as well as royalties on ex-U.S. net sales. If Relay Therapeutics elects not to opt in, then Relay will be eligible to receive up to $695 million in additional development, commercialization and sales-based milestones, as well as royalties on global net sales, anticipated to be in the low-to-mid-teens. In the event of regulatory approval of both RLY-1971 and GDC-6036 in combination, Relay Therapeutics is eligible to receive additional royalties. Relay Therapeutics retains the right to combine RLY-1971 with its selective FGFR2 and mutant-selective PI3Kα programs.

With the execution of this collaboration, Relay Therapeutics anticipates it will have cash and investments to sustain its operations through 2024.

Conference Call Information

Relay Therapeutics will host a live webcast today beginning at 8:00 a.m. ET to discuss the collaboration. To access the live call, please dial 1 (833) 540-1168 (domestic) or 1 (929) 517-0359 (international) and refer to conference ID 8792127. A webcast of the conference call will be available under "News and Presentations" in the Investors & Media section of Relay Therapeutics’ website at View Source The archived webcast will be available on Relay Therapeutics’ website approximately two hours after the conference call and will be available for 30 days following the call.

About RLY-1971

RLY-1971 is a potent small molecule inhibitor of Src homology region 2 domain-containing phosphatase-2 (SHP2). SHP2 is a critical signaling node and regulator that promotes cancer cell survival and growth through the RAS pathway, playing a key role in the way cancer cells develop resistance to targeted therapies. Preclinically, RLY-1971 demonstrated significant anti-tumor activity as a monotherapy in cancers with specific alterations as well as in combination with other anti-tumor agents, potentially overcoming or delaying the onset of resistance to those therapies. RLY-1971 is currently being evaluated in a first-in-human trial designed to treat patients with advanced or metastatic solid tumors. To learn more about the first-in-human clinical trial of RLY-1971, please visit here.