On July 27, 2020 TCR2 Therapeutics Inc. (Nasdaq: TCRR) ("TCR2" or the "Company"), a clinical-stage immunotherapy company with a pipeline of novel T cell therapies for patients suffering from cancer, reported that it has commenced an underwritten public offering of 6,000,000 shares of its common stock (Press release, TCR2 Therapeutics, JUL 27, 2020, View Source [SID1234562645]). TCR2 also intends to grant the underwriters a 30-day option to purchase up to an additional 900,000 shares of common stock. All of the shares in the proposed offering are to be sold by TCR2. The proposed offering is subject to market and other conditions, and there can be no assurance as to whether or when the proposed offering may be completed, or as to the actual size or terms of the proposed offering.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Jefferies, SVB Leerink, Piper Sandler and BMO Capital Markets are acting as joint book-running managers for the offering. SunTrust Robinson Humphrey is acting as co-manager for the offering.

TCR2 intends to use the net proceeds of the offering to advance its clinical and earlier stage programs and for research and development, working capital and general corporate purposes.

The securities described may be offered pursuant to a shelf registration statement on Form S-3 (File No. 333-236965), including a base prospectus that was declared effective by the U.S. Securities and Exchange Commission (the "SEC") on April 28, 2020. The proposed offering will be made only by means of a prospectus. A preliminary prospectus supplement and a final prospectus supplement relating to, and describing the terms of, this offering will be filed with the SEC and will be available on the SEC’s website at www.sec.gov. When available, copies of the preliminary prospectus may also be obtained from: Jefferies LLC, Attention: Equity Syndicate Prospectus Departments, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by phone at (877) 821-7388, or by email at [email protected]; SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA, 02110, by email at [email protected], or by phone at (800) 808-7525, ext. 6218; Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, Minnesota 55402, by email at [email protected], or by phone at (800) 747-3924; or BMO Capital Markets Corp., Attention: Equity Syndicate Department, 3 Times Square, 25th Floor, New York, NY 10036, by email at [email protected], or by phone at (800) 414-3627.

Important Information

This press release shall not constitute an offer to sell or a solicitation of an offer to buy, nor shall there be any offer or 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 July 27, 2020 Lynk Pharmaceuticals (Hangzhou, China) reported that exclusive licensing agreements with Kobe University (Kobe, Japan) and with RIKEN Research Institute (Saitama, Japan) to develop RAS inhibitors with a novel MOA (Press release, Lynk Pharma, JUL 27, 2020, View Source [SID1234562459]). The agreement with Kobe University also includes a joint collaboration which will continue to provide screening and structural support.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

RAS has been identified as a key driver in numerous cancers including pancreatic (95%), colon (50%) and lung adenocarcinomas (30%). RAS was first identified in the 1960’s and has been targeted for over 35 years with only limited success. While recent progress made by irreversible binding towards KRAS G12C subset, this approach cannot inhibit other more dominant KRAS mutants such as G12V and G12D.

Built on Kobe University and RIKEN’s early structural biology and screening outcome, Lynk Pharmaceuticals will utilize its medicinal chemistry and drug design expertise to develop RAS inhibitors with desirable properties to target a broader range of undruggable RAS onco-drivers and ultimately develop the compounds for clinical use. "This is a very ambitious approach for us to challenge a decades-old undruggable target, but we believe our approach, with an exciting novel mechanism of action, will bring better hope to the patients by jointing hands with two reputed research organizations in the world," said Dr. Zhao-Kui (ZK) Wan, Founder, Chairman and CEO of Lynk.

On July 27, 2020 CRISPR Therapeutics (Nasdaq: CRSP), a biopharmaceutical company focused on creating transformative gene-based medicines for serious diseases, reported financial results for the second quarter ended June 30, 2020 (Press release, CRISPR Therapeutics, JUL 27, 2020, View Source [SID1234562456]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We continue to make substantial progress driving our multiple, ongoing clinical development programs. Enrollment in our immuno-oncology trials is ongoing, and we’ve re-initiated dosing in our CTX001 trials," said Samarth Kulkarni, Ph.D., Chief Executive Officer of CRISPR Therapeutics. "Further, we expect to report data from our CTX001 program targeting hemoglobinopathies and our CTX110 program later this year. Despite the challenges posed by COVID-19, we continue to execute on our programs and remain focused on our commitment to patients and their families."

Recent Highlights and Outlook

Beta Thalassemia and Sickle Cell Disease

CRISPR Therapeutics and its partner Vertex provided new clinical data at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress from the two ongoing Phase 1/2 studies of the investigational CRISPR/Cas9 gene-editing therapy CTX001 in patients with transfusion-dependent beta thalassemia (TDT) and in patients with severe sickle cell disease (SCD). Data from two TDT patients demonstrated clinical proof-of-concept for CTX001 in this disease, and longer duration data from one SCD patient showed durable effects on fetal hemoglobin (HbF) levels and the patient was free of vaso-occlusive crises. Screening, enrollment and mobilization in these studies are ongoing; conditioning and dosing have been resumed following temporary COVID-19-related pauses in both studies. CRISPR Therapeutics and Vertex expect to report data from additional patients in the second half of 2020.

In May, CRISPR Therapeutics and its partner Vertex announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to CTX001, an investigational, autologous, gene-edited hematopoietic stem cell therapy, for the treatment of TDT and SCD. In addition to RMAT designation, CTX001 has received Orphan Drug Designation from the U.S. FDA for TDT and SCD and from the European Commission for TDT and SCD. CTX001 also has Fast Track Designation from the U.S. FDA for both TDT and SCD.

Immuno-Oncology

Patient dosing continues in a clinical trial to assess the safety and efficacy of CTX110, CRISPR Therapeutics’ wholly-owned allogeneic CAR-T cell therapy targeting relapsed or refractory CD19+ B-cell malignancies. The Company expects to report top-line data for CTX110 at the end of 2020.

Patient dosing continues in a clinical trial to assess the safety and efficacy of CTX120, CRISPR Therapeutics’ wholly-owned allogeneic CAR-T cell therapy targeting BCMA for the treatment of relapsed or refractory multiple myeloma.

Two independent clinical trials assessing the safety and efficacy of CTX130, CRISPR Therapeutics’ wholly-owned allogeneic CAR-T cell therapy targeting CD70 for the treatment of both solid tumors and certain hematologic malignancies, are open for enrollment.

Other Corporate Matters

In June, CRISPR Therapeutics announced the pricing of an underwritten public offering of 6,428,572 common shares at a public offering price of $70.00 per share, plus the exercise in full of the underwriters’ option to purchase 964,285 additional common shares. Gross proceeds from the offering (including the exercise of the underwriters’ option), before deducting underwriting discounts and commissions and other offering expenses, were $517.5 million. The common stock offering and the option to purchase additional shares closed in July 2020.

CRISPR Therapeutics reported a research agreement with UHN, Canada’s largest research hospital, affiliated with the University of Toronto, and a member of the Toronto Academic Health Science Network. Through UHN’s McEwen Stem Cell Institute, the aim of the collaboration is to combine CRISPR Therapeutics’ gene editing technology with UHN’s methods for differentiating stem cells into hepatocytes at high yield and purity, with the goal of developing regenerative medicine cell therapies for a number of different diseases. The agreement provides CRISPR Therapeutics an option to commercialize the technology.

In June, CRISPR Therapeutics presented four posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Virtual Annual Meeting II. The posters addressed the potential of CRISPR-modified CAR-T cells as follows: an assessment of CRISPR-modified CAR-T cells in patients with non-small cell lung cancer; functionality in vivo and in vitro of allogeneic CAR-T cell products containing multiple CRISPR/Cas9 gene edits; assessment of allogeneic anti-PTK7 CAR-T cells for the treatment of solid tumors; and the potential of CRISPR/Cas9-generated anti-CD70 allogeneic CAR-T cells to target T cell lymphomas.

CRISPR Therapeutics reported it entered into a lease agreement with Breakthrough Properties for a new location in Boston, Massachusetts. The new facility will consolidate CRISPR’s various office and laboratory locations in the greater Boston area into a single location and support the Company’s anticipated future growth for five to seven years from the date of occupancy, which is expected in 2022.

In June, CRISPR Therapeutics announced that it is building a new cell therapy manufacturing facility in Framingham, Massachusetts, for clinical and commercial production of the Company’s investigational cell therapy product candidates. The facility is being designed to provide GMP manufacturing according to FDA and European Medicines Agency (EMA) regulations and guidelines to support clinical supply and commercial product upon potential regulatory approval.
Second Quarter 2020 Financial Results

Cash Position: Cash and cash equivalents as of June 30, 2020 were $945.1 million compared to $889.7 million as of March 31, 2020, an increase of $55.4 million. The increase in cash was primarily driven by financing activities during the quarter of $89.5 million and the $25.0 million milestone received from Vertex in April. The increase was offset by cash used in operating activities during the quarter of $54.3 million (exclusive of the $25.0 million milestone received by Vertex in April) to support spending on the Company’s clinical and pre-clinical programs, as well as payroll and payroll-related expenses to support growth. After including the $484.8 million in net proceeds from our underwritten public offering completed in July, pro forma cash exceeds $1.4 billion.

Revenue: Total collaboration revenue was less than $0.1 million for the second quarter of 2020 compared to $0.3 million for second quarter of 2019. Collaboration revenue primarily consisted of charges to partners for research activities.

R&D Expenses: R&D expenses were $59.4 million for the second quarter of 2020 compared to $39.5 million for the second quarter of 2019. The increase in expenses was driven by increased headcount and development activities supporting the advancement of the hemoglobinopathies program and wholly-owned immuno-oncology programs.

G&A Expenses: General and administrative expenses were $21.4 million for the second quarter of 2020 compared to $15.8 million for the second quarter of 2019. The increase in general and administrative expenses for the year was driven by headcount-related expense and higher facilities cost.

Net Loss: Net loss was $79.7 million for the second quarter of 2020 compared to net loss of $53.7 million for the second quarter of 2019.
About CTX001
CTX001 is an investigational ex vivo CRISPR gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD in which a patient’s hematopoietic stem cells are engineered to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth and is then replaced by the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for TDT patients and painful and debilitating sickle crises for SCD patients.

CTX001 is being developed under a co-development and co-commercialization agreement between CRISPR Therapeutics and Vertex.

About CTX110
CTX110 is a healthy donor-derived gene-edited allogeneic CAR-T therapy targeting cluster differentiation 19, or CD19, for the treatment of CD19+ malignancies. A wholly-owned asset of CRISPR Therapeutics, CTX110 is being investigated in a clinical trial designed to assess the safety and efficacy of CTX110 for the treatment of relapsed or refractory B-cell malignancies. The multi-center, open-label clinical trial is designed to enroll up to 131 patients and investigate several dose levels of CTX110.

About CTX120
CTX120 is a healthy donor-derived gene-edited allogeneic CAR-T therapy targeting B-cell maturation antigen, or BCMA. A wholly-owned asset of CRISPR Therapeutics, CTX120 is being investigated in a clinical trial designed to assess the safety and efficacy of CTX120 for the treatment of relapsed or refractory multiple myeloma. The multi-center, open-label clinical trial is designed to enroll up to 88 patients and investigate several dose levels of CTX120.

About CTX130
CTX130 is a healthy donor-derived gene-edited allogeneic CAR-T therapy targeting cluster of differentiation 70, or CD70, an antigen expressed on various solid tumors and hematologic malignancies. CTX130 is being developed for the treatment of both solid tumors, such as renal cell carcinoma, and T-cell and B-cell hematologic malignancies. A wholly-owned asset of CRISPR Therapeutics, CTX130 is being investigated in two independent clinical trials that are designed to assess the safety and efficacy of CTX130 for the treatment of relapsed or refractory renal cell carcinoma and various subtypes of lymphoma, respectively. The multi-center, open-label clinical trial investigating CTX130 for the treatment of relapsed or refractory renal cell carcinoma is designed to enroll approximately 95 patients and investigate several dose levels of CTX130. The multi-center, open-label clinical trial investigating CTX130 for the treatment of various lymphomas is designed to enroll approximately 46 patients and investigate several dose levels of CTX130.

On July 27, 2020 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB) a late-stage clinical biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer,reported the acceptance of five oral presentations at the International Society of Pediatric Oncology ("SIOP") Virtual Annual Congress held October 14 through October 17, 2020 in Ottawa, Canada (Press release, Y-mAbs Therapeutics, JUL 27, 2020, View Source [SID1234562454]). The abstracts are publicly available online at View Source

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Naxitamab

The abstracts include the following presentations of naxitamab, one of the Company’s lead product candidates, which is currently being evaluated for the treatment of pediatric patients with relapsed or refractory high-risk neuroblastoma, osteosarcoma and other GD2-positive tumors:

"High-dose naxitamab (humanized-3F8) plus stepped-up dosing of granulocyte-macrophage colony-stimulating factor (GM-CSF) for resistant osteomedullary neuroblastoma: major responses and outpatient treatment in a Phase II trial," submitted by MSK in New York

"Naxitamab-based chemoimmunotherapy for resistant high-risk neuroblastoma: preliminary results of HITS treatment," submitted by SJD Barcelona Children’s Hospital in Barcelona, Spain

"Telemedicine blood pressure monitoring after anti-GD2 monoclonal antibody immunotherapy during the COVID-19 pandemic," submitted by MSK in New York
Naxitamab has been accepted for priority review by the U.S. Food and Drug Administration ("FDA") for the treatment of patients with relapsed/refractory high-risk neuroblastoma. The FDA set an action date of November 30, 2020, under the Prescription Drug User Fee Act ("PDUFA").

Omburtamab

The abstracts also include the following presentation of omburtamab, the Company’s other lead product candidate, which is currently being evaluated for the treatment of patients with CNS/Leptomeningeal metastasis from neuroblastoma, diffuse intrinsic pontine glioma ("DIPG"), and desmoplastic small round cell tumors ("DSRCT"):

"Intracerebroventricular radioimmunotherapy using 131I-omburtamab for neuroblastoma central nervous system/leptomeningeal metastases, interim results from multi-center trial 101," submitted by Memorial Sloan Kettering Cancer Center ("MSK") in New York
During June 2020, we initiated the submission of the Biologics License Application ("BLA") for omburtamab under the FDA’s Rolling Review process and completion of the BLA submission is currently expected to take place over the next few weeks.

GD2-GD3 Vaccine

The abstracts also include the following presentation of the GD2-GD3 Vaccine, the Company’s vaccine candidate, which is currently being evaluated for high-risk neuroblastoma patients in remission:

"Favorable toxicity profile of bivalent GD2/GD3 neuroblastoma vaccine," submitted by MSK in New York

On July 27, 2020 CARISMA Therapeutics Inc., a biopharmaceutical company focused on discovering and developing innovative immunotherapies, reported that the U.S. Food and Drug Administration (FDA) has cleared an investigational new drug (IND) application for the Company’s lead product candidate, CT-0508, an anti-human epidermal growth factor receptor 2 (HER2) targeted chimeric antigen receptor macrophage (CAR-M) (Press release, Carisma Therapeutics, JUL 27, 2020, View Source [SID1234562419]). Under this IND, CARISMA intends to initiate its Phase 1, first-in-human, multi-center study in patients with recurrent or metastatic HER2 overexpressing solid tumors after failure of approved HER2 targeted agents.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"This will be the first time that an engineered macrophage has progressed successfully to the in-patient study phase and represents a new chapter for CARISMA: advancing from a preclinical discovery-stage company to a clinical development stage company," said Steven Kelly, President and Chief Executive Officer. "The clearance of our IND application for CT-0508 is a ground-breaking milestone in the field of cell-based cancer immunotherapy."

Historically, cell therapies have encountered key challenges treating solid tumors, including limited trafficking to the tumor site, an immunosuppressive tumor microenvironment, and the heterogeneous expression of tumor-associated antigens, but CARISMA’s preclinical findings suggest that CAR-M therapy could overcome these challenges.

"Our preclinical findings indicate that CAR-M have the ability to mount a broad immune response against cancers, and the acceptance of the CT-0508 IND brings this technology to patients with incurable solid tumors," said Michael Klichinsky, PharmD, PhD, co-inventor of the CAR-M technology, Scientific Co-founder, and Vice President of Discovery at CARISMA Therapeutics.

CARISMA Scientific Co-founder and Assistant Professor of Hematology-Oncology in Penn’s Abramson Cancer Center, Saar Gill, MD, PhD, added, "I’m incredibly pleased and excited to see the technology that was originally developed in my lab progress to the clinic. Getting a chance to translate your preclinical research and evaluate its potential impact for patients is the reason why I do this type of work."

The planned clinical trial will be conducted at two trial sites—University of Pennsylvania in Philadelphia, Pennsylvania, and University of North Carolina in Chapel Hill, North Carolina—and will enroll patients with different types of recurrent or metastatic cancers with HER2 overexpressing solid tumors.

"HER2 is overexpressed not only in breast and gastroesophageal cancers, but in a wide variety of epithelial origin solid tumors, such as non-small cell lung, colorectal, bladder, and pancreatic cancers," said Debora Barton, MD, Chief Medical Officer at CARISMA Therapeutics. "There is an important unmet medical need that remains to be addressed and we aim to achieve that during this clinical trial."

Corporate Developments

CARISMA also announced today the expansion of its Board of Directors to include Briggs W. Morrison, MD, as well as additions to the Scientific Advisory Board, Nina Bhardwaj, MD, PhD, and Prasad S. Adusumilli, MD.

"CARISMA is at an exciting juncture," said Mike Heffernan, Chairman of the Board of Directors. "Evolving from a preclinical stage company, having demonstrated reduced tumor burden and significantly improved overall survival with our CAR-M technology in humanized mouse models, to quickly approaching the in-clinic study of this first-of-its-kind therapy. We are eager to have Drs. Morrison, Bhardwaj and Adusumilli’s counsel as CARISMA embarks on this new chapter."

The CARISMA Board of Directors welcomes Dr. Briggs Morrison, who brings with him over 25 years of pharmaceutical, global regulatory and business development leadership experience. Joining the Scientific Advisory Board are Drs. Nina Bhardwaj and Prasad S. Adusumilli. Dr. Bhardwaj brings extensive immunology experience: she is currently the Director of Immunotherapy, Medical Director of the Vaccine and Cell Therapy Laboratory, and Co-Director of the Cancer Immunology Program at The Tisch Cancer Institute and holds the Ward Coleman Chair in Cancer Research. She has made influential contributions to human dendritic cell biology, specifically regarding isolation, biology, antigen presenting function and use as vaccine adjuvants in humans. Dr. Adusumilli, Deputy Chief of Thoracic Service at Memorial Sloan Kettering Cancer Center, brings his extensive experience with the investigation of the tumor immune microenvironment and the development of CAR T-cell-mediated immunotherapies.