On April 1, 2019 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage immunotherapy company developing the next generation of novel T cell therapies for patients suffering from cancer, reported financial results for the fourth quarter and full year ended December 31, 2018 and provided a corporate update (Press release, TCR2 Therapeutics, APR 1, 2019, View Source [SID1234534865]).

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"TCR2 has achieved important scientific, clinical, and operational milestones over the past year," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "Although adoptive T cell therapies have made significant progress in the fight against cancer, our TRuC platform has the potential to both improve upon existing options and expand their use. TC-210 has cleared its IND and we have initiated our Phase 1/2 clinical trial, with initial data expected later this year. We also remain on track to submit an IND for TC-110 in the second half of 2019. In February, we successfully completed our initial public offering, a significant step for the Company which further strengthened our financial position."

2018 Corporate Highlights

Advanced TC-210, TCR2’s lead T cell receptor (TCR) Fusion Construct T cell (TRuC T cell) product candidate, to investigational new drug (IND) application submission in December 2018 and IND clearance by the U.S. Food and Drug Administration (FDA) in January 2019. TCR2 engineered TC-210 T cells to target and kill mesothelin-expressing cancers while engaging the entire TCR, independent of human leukocyte antigens (HLA). In preclinical studies, TC-210 has demonstrated better anti-tumor activity, longer persistence, and lower cytokine release compared to chimeric antigen receptor (CAR)-T cells engineered with the same mesothelin binder. TCR2 initiated a Phase 1/2 clinical trial for TC-210 to treat patients with mesothelin-positive solid tumors, including non-small cell lung cancer (NSCLC), ovarian cancer, malignant pleural/peritoneal mesothelioma, and cholangiocarcinoma. TCR2 expects to generate its first clinical data for TC-210 in the second half of 2019.

Expanded the TCR2 pipeline, initiating IND-enabling studies for TC-110 and TC-220 product candidates, and building next-generation enhancements into the TRuC platform.

TC-110 is a CD19 targeted TRuC-T cell product candidate designed to treat patients with CD19-positive B-cell hematological malignancies, including diffuse large B-cell lymphoma (DLBCL), adult acute lymphoblastic leukemia (aALL), follicular lymphoma (FL), and other non-Hodgkin lymphoma (NHL) subtypes. In preclinical studies, TC-110 has shown better anti-tumor activity and persistence compared to CD28 and 4-1BB CAR-T cells engineered with the same CD19 binder, while also exhibiting lower levels of cytokine release.

TC-220 is a MUC16 (Mucin 16, Cell Surface Associated)-targeted TRuC-T cell product candidate designed to treat patients with MUC16-positive solid tumors. MUC16 is highly expressed in many solid tumors, including ovarian, pancreatic, gastric, and colorectal cancers. TC-220 has shown strong anti-tumor activity in preclinical models of MUC16-positive ovarian cancers. TCR2 plans to file an IND for TC-220 in the first half of 2020.

TCR2 is developing several additional tools that may be incorporated into future TRuC product candidates to overcome tumor defense mechanisms, including dual-antigen targeting and strategies to counter the immunosuppressive microenvironment of solid tumors. TCR2 is also evaluating multiple proprietary designs for allogeneic, or off the shelf, TRuC-T cells.

Established semi-automated Good Manufacturing Practice (GMP) manufacturing process. TCR2 currently manufactures GMP-grade clinical lots for TC-210 through third-party contractors. In December 2018, TCR2 entered into an agreement with Cell and Gene Therapy (CGT) Catapult Limited (Catapult), which will allow TCR2 to manufacture TRuC-T cells using its own personnel at CGT Catapult’s facility in Stevenage, UK. The TCR2 CGT Catapult facility is expected to be operational in the second half of 2019. At full capacity, TCR2 estimates this facility would expand its manufacturing capacity to a total of approximately 400 treatments per year.

Raised $125 million in an oversubscribed Series B financing round in March 2018. The financing was co-led by 6 Dimensions Capital and Curative Ventures with participation from new investors Redmile and Arrowmark and all of TCR2’s Series A investors.

Strengthened its management and board in 2018. This included adding Ian Somaiya as Chief Financial Officer, along with Neil Gibson Ph.D. and Andrew Allen M.D., Ph.D. to the Board of Directors.

Recent Developments

In January 2019, the FDA cleared the IND for TC-210. TCR2 initiated its Phase 1/2 trial to treat patients with NSCLC, ovarian cancer, malignant pleural/peritoneal mesothelioma, and cholangiocarcinoma. TCR2 expects to generate initial data from the trial in the second half of 2019.

In February 2019, TCR2 completed an initial public offering pursuant to which it issued and sold 5,750,000 shares of common stock, including full exercise of the underwriters’ over-allotment option, resulting in net proceeds of $80.2 million after deducting underwriting discounts and commissions and other offering expenses.

In February 2019, the FDA granted orphan drug designation to TC-210 for the treatment of mesothelioma.

TCR2 recently held a pre-IND meeting with the FDA and remains on track to submit an IND for TC-110 in the second half of 2019.

In February 2019, the United States Patent and Trademark Office issued U.S. Patent No.: 10,208,285, with claims covering TCR2’s TRuC-T cells that express anti-mesothelin TCR fusion proteins, including TC-210.

Anticipated Milestones
TCR2 plans to advance its first three TRuC-T cell product candidates into clinical trials by the first half of 2020, while also establishing and expanding its manufacturing capabilities through its collaboration with CGT Catapult.

TC-210 – release initial Phase 1 data from the Phase 1/2 trial in 2H 2019.

TC-110 – IND submission in 2H 2019.

TC-220 – IND submission in 1H 2020.

Catapult manufacturing facility – operational in 2H 2019.

Financial Highlights

TCR2 ended 2018 with $123.2 million in cash, cash equivalents, and investments compared to $19.8 million as of December 31, 2017. Net cash from financing activities for the year ended December 31, 2018 was $123.0 million compared to $16.2 for the year ended December 31, 2017. Net cash used in operations was $18.8 million for the year ended December 31, 2018 compared to $12.0 million for the year ended December 31, 2017.

Net loss for the year ended December 31, 2018 was $24.3 million compared to $13.1 million for the year ended December 31, 2017.

Research and development expenses were $19.7 million for the year ended December 31, 2018 compared to $9.6 million for the year ended December 31, 2017. The increase in R&D expenses is primarily related to increase in headcount and preclinical development of our lead solid tumor product candidate, TC-210.
General and administrative expenses were $6.8 million for the year ended December 31, 2018, compared to $3.6 million for the year ended December 31, 2017. The increase in general and administrative expenses was primarily due to an increase in personnel costs.

Upcoming Events
Members of the TCR2 Therapeutics management team are scheduled to present at the following upcoming conferences.

Jefferies Immuno-Oncology Cell Therapy Summit: Alfonso Quintás Cardama, M.D., Chief Medical Officer, will present on Friday, April 5, 2019 at 7:30am in Boston, MA.

4th Annual CAR-T Congress USA: Robert Hofmeister Ph.D., Chief Scientific Officer, will present on Wednesday, April 17, 2019 at 9:40am in Boston, MA.

Class of 2018 Biotech IPOs Investor Day: Ian Somaiya, Chief Financial Officer, will present on Friday, April 26, 2019 at the offices of Davis Polk in New York, NY.

BioTrinity 2019: Garry Menzel, Ph.D., President and CEO, will present on Tuesday, April 30, 2019 in London, UK

On April 1, 2019 Cytori Therapeutics (NASDAQ: CYTX) ("Cytori" or the "Company") reported its fourth quarter and year-end 2018 financial results and provided updates on corporate activities (Press release, Cytori Therapeutics, APR 1, 2019, View Source [SID1234534864]). Also announced was a transaction to divest certain cell therapy assets to Lorem Vascular of Melbourne, Australia yielding $4MM in non-dilutive funding to the Company .

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Fourth quarter 2018 net loss was $2.2 million, or $0.16 per share. Operating cash burn for the fourth quarter of 2018 was approximately $2.5 million. Cytori ended the year with approximately $5.3 million of cash and cash equivalents.

"This transaction sale accomplishes a number of important objectives for the company," said Dr. Marc Hedrick, Cytori President & Chief Executive Officer. "Most critically it allows us to further increase the focus on our clinical stage oncology pipeline while bringing in non-dilutive capital. We also are able to maintain our most valuable cell therapy assets, including Japan that has a forthcoming trial readout in our ADRESU trial."

Our lead clinical stage asset, Doxorubicin Hydrochloride Cytori, formerly called ATI-0918, is an important potential therapy for Breast and Ovarian Cancer, Multiple Myeloma and Kaposi’s Sarcoma. Our current development program is focused in Europe where we believe there is a potential market opportunity of $120 million annually. In Q1 2019, Cytori submitted a letter of intent to file a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) for Doxorubicin Hydrochloride Cytori. Doxorubicin Hydrochloride Cytori is being developed as a generic version of Janssen’s Caelyx pegylated liposomal doxorubicin. The Company continues to evaluate potential development and commercialization partnering opportunities for Doxorubicin Hydrochloride Cytori with a focus on Europe and China. European approval and launch of Doxorubicin Hydrochloride Cytori is projected to be in late 2020.

Our second clinical stage oncology focused asset is ATI-1123, a phase II ready, patented, albumin-stabilized pegylated liposomal docetaxel. In 2018, the Company received an orphan drug designation from the U.S. FDA for the indication of small cell lung cancer and is pursuing a 505(b)(2) new drug application (NDA) pathway in the U.S. which may offer an accelerated clinical timeline and lower development cost. The Company is exploring near term development strategies and intends to advance this program aggressively in 2019.

Cytori’s ADRESU pivotal urinary incontinence trial using Cytori Cell Therapy has completed enrollment and anticipates data read out in the second quarter of 2019. If the data is positive, Cytori intends to seek expedited approval and reimbursement for the Japanese market for this indication. In Q1 2019, Cytori received approval from the United States Food & Drug Administration to expand the enrollment criteria for its RELIEF clinical trial of intravenously delivered Cytori Cell Therapy for patients with severe burn injuries.

Q4 2018 and Full Year 2018 Financial Performance

Q4 2018 and full year operating cash burn was $2.5 million and $12.0 million, compared to $4.2 million and $18.1 million for the same periods in 2017, respectively.
Q4 2018 and full year product revenues were $0.4 million and $2.7 million, compared to $0.7 million and $2.7 million for the same periods in 2017, respectively.
Q4 2018 and full year contract revenues were $0.7 million and $3.0 million, compared to $0.9 million and $3.7 million for the same periods in 2017, respectively.
Cash and debt principal balances at December 31, 2018 were approximately $5.3 million and $13.0 million, respectively.
Q4 2018 adjusted net loss was $2.8 million or $0.20 per share, compared to a net loss of $4.3 million or $1.00 per share for the same period in 2017. The adjusted net loss excludes a non-cash beneficial conversion feature (a non gaap measure) related to the issuance of our Series C convertible preferred shares in the third quarter of 2018 of $2.5 million, as well as a credit of $0.6 million related to a change in fair value of warrant liability (a non gaap measure). Q4 2018 net loss allocable to common stockholders was $2.2 million, or $0.16 per share.
Full year 2018 adjusted net loss was $14.9 million or $1.71 per share, compared to $21.0 million or $6.48 per share for the same period in 2017. The adjusted net loss excludes a non-cash beneficial conversion feature (a non gaap measure) related to the issuance of our Series C convertible preferred shares in the third quarter of 2018 of $2.5 million, as well as a credit of $2.2 million related to a change in fair value of warrant liability (a non gaap measure). Full year 2018 net loss allocable to common stockholders was $15.1 million, or $1.74 per share.
Selected Key Anticipated Milestones:

Doxorubicin Hydrochloride Cytori: File Market Authorization Application to the European Medicines Agency in late 2019 or early 2020.
ATI-1123: Clarify the FDA 505(b)(2) pathway applicability and announce clinical development plan in mid 2019.
Cell Therapy Japan: Report ADRESU urinary incontinence pivotal clinical trial results in Q2 2019.
Management Conference Call Webcast

Cytori will host a management conference call at 5:30 p.m. Eastern Time today to further discuss its progress. The webcast will be available live and by replay two hours after the call and may be accessed under "Webcasts" in the Investor Relations section of Cytori’s website. If you are unable to access the webcast, you may dial in to the call at +1.877.402.3914, Conference ID: 8766078.

On April 1, 2019 Sierra Oncology, Inc. (Nasdaq: SRRA), a clinical stage drug development company focused on advancing targeted therapeutics for the treatment of patients with significant unmet needs in hematology and oncology, reported that preclinical data for SRA737+LDG, its Chk1 inhibitor plus non-cytotoxic low dose gemcitabine (LDG), in combination with immunotherapy, are being reported today in a late-breaking oral presentation at the American Association of Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019 being held in Atlanta, Georgia (Press release, Sierra Oncology, APR 1, 2019, View Source [SID1234534861]).

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"Given the limited response rates for anti-PD-L1 drugs in patients with small cell lung cancer (SCLC), better treatment options are sorely needed. Our data, showing durable tumor regressions when combining SRA737+LDG with anti-PD-L1 in a mouse model, warrant further clinical studies to investigate the potential of this approach as a strategy to improve outcomes in our patients," said senior researcher Lauren Averett Byers, M.D., Associate Professor of Thoracic/Head and Neck Medical Oncology at The University of Texas MD Anderson Cancer Center, Houston, Texas.

In the study, SRA737+LDG demonstrated significant anti-tumor activity when combined with anti-PD-L1 in a mouse model of SCLC, resulting in durable tumor regressions. These results were accompanied by an induction of anti-tumor cytotoxic T-cells and M1 macrophages and a corresponding reduction in several pro-tumorigenic cell types in the tumors of drug-treated animals.

"The unique replication stress-inducing properties of SRA737 as potentiated by non-cytotoxic low dose gemcitabine have been previously demonstrated to result in intrinsic anti-tumor activity in multiple preclinical models. These striking new data provide evidence for SRA737+LDG’s activation of innate immune signaling and the establishment of an anti-tumor immune microenvironment that synergizes with immune checkpoint inhibitors," said Dr. Christian Hassig, Chief Scientific Officer, Sierra Oncology. "These findings provide a mechanistic basis for the growing body of evidence highlighting a synergistic interplay between replication stress and anti-tumor immune responses and afford a compelling rationale for evaluating SRA737+LDG with immunotherapy in the clinic."

SRA737 AACR (Free AACR Whitepaper) Late-Breaking Oral Presentation:
Date/Time: Monday, April 1st from 3:00 to 5:00 pm ET
Session: Minisymposium: Late-Breaking Research 2
Title: Combination treatment of the CHK1 inhibitor, SRA737, and low dose gemcitabine demonstrates profound synergy with anti-PD-L1 inducing durable tumor regressions and modulating the immune microenvironment in small cell lung cancer
Authors: Triparna Sen, Carminia M. Della Corte, Snezana Milutinovic, Lixia Diao, Robert J Cardnell, Ryan J. Hansen, Bryan Strouse, Michael P. Hedrick, Christian Hassig, Jing Wang, Lauren A Byers.
Location: Georgia World Congress Center, Room B404

Summary slides from this presentation will be made available on the company’s website at www.sierraoncology.com

About SRA737+LDG
SRA737 is a potent, highly selective, orally bioavailable small molecule inhibitor of Checkpoint kinase 1 (Chk1), a key regulator of cell cycle progression and the DNA Damage Response (DDR). SRA737+LDG is a novel drug combination, where non-cytotoxic low dose gemcitabine acts as a potent inducer of replication stress that potentiates SRA737’s anti-tumor activity.

Phase 1/2 clinical trials of SRA737 as monotherapy (NCT02797964) and in combination with low dose gemcitabine (NCT02797977) in multiple solid tumors (ovarian, prostate, non-small cell lung, squamous (head & neck, anal), colorectal, small cell lung, sarcoma, cervical, anogenital) are ongoing. Sierra has also prepared for a potential clinical study of SRA737 in combination with a PARP inhibitor.

Sierra Oncology retains the global commercialization rights to SRA737.

On April 1, 2019 Vaccibody AS and Nektar Therapeutics (Nasdaq: NKTR) reported the presentation of new preclinical data for VB10.NEO, a personalized neoantigen cancer vaccine, combined with bempegaldesleukin (NKTR-214 or bempeg), a CD122-preferential IL-2 pathway agonist (Press release, Vaccibody, APR 1, 2019, View Source [SID1234534860]). These data were presented today in a poster session at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019.

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"We are excited to present these novel preclinical data that show combining bempeg with VB10.NEO synergize to increase both the breadth and the depth of the neoantigen-specific immune response. These unique and non-overlapping mechanisms produced an expansion of the VB10.NEO elicited neoantigen-specific T cells and demonstrated enhanced anti-tumor efficacy in mice. We look forward to evaluating this novel immuno-oncology combination in a clinical study in patients with advanced or metastatic squamous cell carcinoma of head and neck later this year," said Agnete B. Fredriksen, Ph.D., Vaccibody’s President and Chief Scientific Officer.

VB10.NEO is designed to specifically activate a patient’s immune system to tumor-specific antigens, called neoantigens. Bempeg is designed to expand and proliferate tumor antigen-specific T cells in the tumor microenvironment. Addition of bempeg to VB10.NEO is intended to drive maximal expansion of vaccine-induced neoantigen-specific T cells for the treatment of cancer.

"Personalized T cell vaccines could play a critical and central role in cancer immunotherapy," said Jonathan Zalevsky, Ph.D., Chief Scientific Officer at Nektar. "These preclinical data highlight the potential of combining a personalized cancer vaccine with a T cell proliferator to induce maximal expansion of vaccine-induced T cell clones and durable responses and specific anti-tumor immunity. We are highly encouraged by these results and look forward to testing this unique approach to personalized cancer treatment in patients with squamous cell carcinoma of the head and neck."

Details of the poster presentation at AACR (Free AACR Whitepaper) are as follows and will be available for download at the time of presentation at View Source and View Source

Abstract #2256
Title: "Combination of neoantigen DNA plasmid vaccine VB10.NEO and NKTR-214, a CD122-biased immunostimulatory cytokine, induces strong neoantigen-specific T cell responses and sustained tumor regression in pre-clinical models"
Session: Clinical Research – Combination Therapies 1
Session Data and Time: Monday, April 1, 2019, 1:00 p.m. – 5:00 p.m. Eastern Time

Combination of VB10.NEO and NKTR-214 synergizes to elicit greater breadth and depth of neoantigen-specific T cell responses than each individual treatment.
The synergistic effect was observed in both CD4 and CD8 T cells, and most pronounced on CD8 T cell responses, further supporting the combination’s potential to induce strong immunogenic CD8+ T cell responses.
VB10.NEO in combination with NKTR-214 and anti-PD-1 induce rapid, complete and durable tumor regression of small tumors and long-lasting stabilization of large tumors supporting the rationale for examining the combination clinically.
In September 2018, Nektar and Vaccibody entered into a clinical collaboration to evaluate bempegaldesleukin in combination with VB10.NEO. A pilot study evaluating the combination in patients with squamous cell carcinoma of the head and neck is planned to begin mid-2019.

About VB10.NEO
VB10.NEO, is a proprietary therapeutic DNA vaccine which uses the patient’s own neoantigens for the personalized treatment of cancer patients. A phase I/IIa neoantigen clinical trial is currently enrolling patients with locally advanced or metastatic melanoma, non-small cell lung carcinoma, clear renal cell carcinoma as well as urothelial cancer or squamous cell carcinoma of the head and neck.

About bempegaldesleukin (NKTR-214)
Bempegaldesleukin is an investigational, first-in-class, CD122-preferential IL-2 pathway agonist designed to provide rapid activation and proliferation of cancer-killing immune cells, known as CD8+ effector T cells and natural killer (NK) cells, without over activating the immune system. Bempegaldesleukin stimulates these cancer-killing immune cells in the body by targeting CD122 receptors found on the surface of these immune cells. CD122, which is also known as the Interleukin-2 receptor beta subunit, is a key signaling receptor that is known to increase proliferation of these effector T cells.1 In clinical and preclinical studies, treatment with bempegaldesleukin resulted in expansion of these cells and mobilization into the tumor micro-environment.2,3 Bempegaldesleukin has an antibody-like dosing regimen similar to the existing checkpoint inhibitor class of approved medicines.

On April 1, 2019 Mirati Therapeutics, Inc. (NASDAQ: MRTX), a clinical stage targeted oncology company, reported that it will present at the H.C. Wainwright & Co. Global Life Sciences Conference in London, England on Monday, April 8th at 11:30am BST/6:30am ET/3:30am PT. Christopher C. LeMasters, Chief Business Officer, will provide a corporate update at the conference (Press release, Mirati, APR 1, 2019, Mirati Therapeutics To Present At The H.C. Wainwright & Co. Global Life Sciences Conference [SID1234534859]).

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The presentations will be webcast and made available through the "Investors" section of www.mirati.com, and replays will be made available for 90 days following the events.