On November 10, 2021 TCR2 Therapeutics Inc. (Nasdaq: TCRR), a clinical-stage cell therapy company with a pipeline of novel T cell therapies for cancer patients suffering from solid tumors, reported financial results for the third quarter ended September 30, 2021 and provided a corporate update (Press release, TCR2 Therapeutics, NOV 10, 2021, View Source [SID1234595218]).

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"Over the last few months, we continue to treat cancer patients in our ongoing gavo-cel Phase 1 clinical trial and have observed meaningful clinical benefit in three different treatment-refractory solid tumor indications," said Garry Menzel, Ph.D., President and Chief Executive Officer of TCR2 Therapeutics. "As we prepare for the phase 2 trial to be launched in early 2022, we are expanding our US manufacturing footprint and successfully negotiated a clinical trial collaboration agreement with Bristol Myers Squibb, where we will have the opportunity to evaluate the efficacy and duration of gavo-cel in combination with Opdivo and Yervoy. We anticipate selecting the RP2D before year end and look forward to providing an update on gavo-cel in 1Q22 following review by the US Food and Drug Administration."

Recent Developments

Gavo-cel:

TCR2 announced positive interim data from the first 17 patients treated in the Phase 1 portion of the gavo-cel Phase 1/2 clinical trial for mesothelin-expressing solid tumors. 15 of the 16 patients evaluable for efficacy experienced regression of their target lesions including 6 patients that achieved a partial response (PR) by target lesion assessment, 4 of whom met criteria for a PR according to RECIST 1.1 criteria. The maximum tolerated dose (MTD) was declared 5×108/m2after lymphodepletion.
Following identification of the MTD, TCR2 announced the completion of the 3-patient cohort at the new dose level 3.5A (3×108/m2 following lymphodepletion) using a split dosing approach. Two patients were evaluable for safety. In both cases, gavo-cel was well-tolerated with no patients experiencing Grade ≥3 cytokine release syndrome (CRS).
TCR2 announced a clinical trial collaboration agreement with Bristol Myers Squibb (NYSE: BMY) to evaluate gavo-cel in combination with Opdivo (nivolumab) and Yervoy (ipilimumab) in its planned Phase 2 clinical trial in treatment refractory mesothelin-expressing solid tumors.
Corporate:

TCR2 announced at its virtual R&D Day on October 20, 2021, its pipeline prioritization of solid tumors and highlighted programs from its emerging TRuC pipeline including TC-510, its first TRuC-T cell enhanced with a PD1xCD28 switch receptor; TC-520, its lead candidate targeting CD70 expressing an IL-15 enhancement; allogeneic TRuC-T cells; and TRuC Tregs, the first utilization of the TRuC platform in the autoimmune setting.
TCR2 announced the expansion of its manufacturing capacity by exercising an option on a second clean room at ElevateBio BaseCamp which adds to the buildout of clinical and commercial supply currently underway at its Rockville, MD facility. In connection with this expansion, TCR2 proposes to cease manufacturing activities at the Cell and Gene Therapy Catapult (CGT Catapult) in Stevenage, UK.
Anticipated Milestones

TCR2 anticipates the identification of the recommended Phase 2 dose (RP2D) in 4Q21.
TCR2 plans to file an IND for TC-510, the first enhanced TRuC-T cell (targeting mesothelin with a PD1xCD28 switch), in the first quarter of 2022.
TCR2 anticipates initiation of IND-enabling studies for TC-520, an enhanced CD70 targeting TRuC-T cell program in 2022.
TCR2 plans to select a lead candidate for its allogeneic program in 2022.
TCR2 anticipates production of clinical trial material from ElevateBio BaseCamp in anticipation of demand from the Phase 2 expansion trial of gavo-cel in 2022.
Financial Highlights

Cash Position: TCR2 ended the third quarter of 2021 with $295.7 million in cash, cash equivalents, and investments compared to $228.0 million as of December 31, 2020. Net cash used in operations was $19.4 million for the third quarter of 2021 compared to $10.8 million for the third quarter of 2020. TCR2 projects net cash use of $100-105 million for 2021, the lower end of the range previously provided. We expect cash on hand to support operations through 2023.

R&D Expenses: Research and development expenses were $20.3 million for the third quarter of 2021 compared to $12.8 million for the third quarter of 2020. The increase in R&D expenses was primarily due to an increase in headcount, additional lab facilities, and manufacturing facilities.

G&A Expenses: General and administrative expenses were $6.0 million for the third quarter of 2021 compared to $4.4 million for the third quarter of 2020. The increase in general and administrative expenses was primarily due to an increase in personnel costs.

Net Loss: Net loss was $26.2 million for the third quarter of 2021 compared to $16.9 million for the third quarter of 2020.
Upcoming Events

TCR2 Therapeutics management is scheduled to participate at the following upcoming conferences.

Jefferies London Healthcare Conference: Garry Menzel, President and Chief Executive Officer of TCR2 Therapeutics, will present an update on Company progress on Tuesday, November 16, 2021 at 12:20pm GMT (7:20am ET)
Piper Sandler 33rd Annual Virtual Healthcare Conference: management will participate in a fireside chat using a virtual platform on Monday, November 22, 2021 at 10:00am ET

On November 10, 2021 Olema Pharmaceuticals, Inc. ("Olema" or "Olema Oncology," Nasdaq: OLMA), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted therapies for women’s cancers, today provided an update on recent company developments and reported third quarter financial results for the period ended September 30, 2021 (Press release, Olema Oncology, NOV 10, 2021, View Source [SID1234595235]).

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"Our team has made great progress advancing OP-1250 through the dose escalation portion of our ongoing Phase 1/2 clinical trial and we look forward to presenting interim pharmacokinetic, safety, tolerability and initial efficacy data at the San Antonio Breast Cancer Symposium in December," said Sean P. Bohen, M.D., Ph.D., President and Chief Executive Officer of Olema Oncology. "We are encouraged by the emerging clinical profile of OP-1250 and plan to initiate Phase 2 monotherapy expansion as well as the first planned Phase 1b combination trial with a CDK4/6 inhibitor in the first quarter of 2022."

"OP-1250 has the potential to be a differentiated, best-in-class complete estrogen receptor (ER) antagonist (CERAN) that we believe could become the backbone endocrine therapy of choice for ER+ breast cancer. As we enroll more patients, we look forward to generating additional clinical data in support of OP-1250’s use both as monotherapy and in combination with other approved breast cancer treatments," continued Dr. Bohen.

Recent Corporate Highlights

●Completed dose escalation in the ongoing Phase 1/2 study of OP-1250 in patients with metastatic, ER+ / HER2- breast cancer.
●Selected the OP-1250 starting dose and initiated preparations for the first planned combination study with a CDK4/6 inhibitor.
●Presented new nonclinical data on OP-1250 at the 1st JCA-AACR Precision Cancer Medicine International Conference held virtually from September 10-12, 2021 (U.S.)
Image result for olema logo

and September 11-12, 2021 (Japan). The poster presentation reviewed a series of nonclinical assessments Olema conducted on a panel of antiestrogens with known chemical structures to evaluate their ability to inhibit ER activity, block breast cancer proliferation and degrade ER receptors.
●Presented a Trials-in-Progress poster at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper), held virtually from October 7-10, 2021. The poster reviewed the design of Olema’s ongoing Phase 1/2 open-label, first-in-human, multicenter, dose-escalation and dose-expansion study evaluating OP-1250 monotherapy in adult subjects with recurrent, locally advanced or metastatic ER+ / HER2- breast cancer (NCT04505826).
●Expanded Olema’s operational footprint with the opening of new office space in Cambridge, Massachusetts.
Anticipated Milestones

●Present interim Phase 1 monotherapy dose escalation data at the 2021 San Antonio Breast Cancer Symposium.
●Initiate dose expansion by year-end with up to two doses. Each cohort will enroll approximately 15 patients with measurable disease, and findings will help inform the selection of a recommended Phase 2 dose (RP2D).
●Initiate Phase 2 in the first quarter of 2022. Preliminary anti-tumor efficacy will be assessed across three cohorts: patients with measurable disease (N=50), patients with non-measurable disease (N=15) and patients with CNS metastasis (N=15).
●Initiate the first Phase 1b clinical trial of OP-1250 in combination with a CDK4/6 inhibitor in the first quarter of 2022.
Financial Highlights

●Cash, cash equivalents and marketable securities as of September 30, 2021 were $306.0 million. Olema anticipates that this balance of cash will be sufficient to fund operations through the end of 2023.
● Net loss for the quarter ended September 30, 2021 was $17.7 million, compared to $7.8 million for the same period of the prior year.
●Research and development (R&D) expenses were $12.5 million for the quarter ended September 30, 2021, compared to $4.7 million for the same period of the prior year. The increase in R&D expenses was primarily related to the advancement of the ongoing Phase 1/2 clinical trial of OP-1250, increase in nonclinical development activities, higher personnel-related expenses and higher non-cash stock-based compensation expenses.
Image result for olema logo

●General and administrative (G&A) expenses were $5.2 million for the quarter ended September 30, 2021, compared to $3.2 million for the same period of the prior year. The increase in G&A expenses was primarily related to an increase in personnel, public company-related expenses, other corporate costs and higher non-cash stock-based compensation expenses.

On November 10, 2021 Mustang Bio, Inc. ("Mustang") (NASDAQ: MBIO), a clinical-stage biopharmaceutical company focused on translating today’s medical breakthroughs in cell and gene therapies into potential cures for hematologic cancers, solid tumors and rare genetic diseases, reported that the company has executed an exclusive license agreement with Leiden University Medical Centre ("LUMC") for a first-in-class ex vivo lentiviral gene therapy for the treatment of RAG1 severe combined immunodeficiency ("RAG1-SCID") (Press release, Mustang Bio, NOV 10, 2021, View Source [SID1234595269]).

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The therapy, which includes low-dose conditioning prior to reinfusion of the patients’ own gene-modified blood stem cells, is currently being evaluated in a Phase 1/2 multicenter clinical trial in Europe. The ongoing clinical trial recently enrolled its first patient, and additional clinical sites are expected to be added in the near future. The RAG1-SCID program has been granted Orphan Drug Designation by the European Medicines Agency.

Mustang also established an ongoing partnership with Frank J. Staal, Ph.D., professor of Molecular Stem Cell Biology and molecular immunologist, whose laboratory developed the therapy. Dr. Staal will continue the development of additional lentiviral gene therapies in his lab, to which Mustang Bio has rights under the agreement.

The RAG1-SCID therapy expands the pipeline of ex vivo lentiviral gene therapies currently in development at Mustang. The Company’s lead programs, MB-107 and MB-207, are being investigated for the treatment of X-linked severe combined immunodeficiency ("XSCID"). A pivotal multicenter trial studying MB-107 is expected to enroll its first patient in the first quarter of 2022. XSCID and RAG1-SCID make up almost 60% of all SCID cases1 combined.

Manuel Litchman, M.D., President and Chief Executive Officer of Mustang said, "We are excited to add RAG1-SCID to the Mustang portfolio as it enables us to leverage our lentiviral gene therapy expertise and experience and our state-of-the-art cell processing facility. Mustang is establishing itself as the leader in developing treatments for patients with severe combined immunodeficiency, an area of high unmet need. We have made great progress in moving our XSCID therapy into a registrational trial and look forward to similarly advancing this RAG1-SCID therapy to make it available for patients in need of life-saving treatment."

About RAG1-SCID
Severe combined immunodeficiency (SCID) due to complete recombinase-activating gene-1 (RAG1) deficiency is a rare, genetic severe combined immunodeficiency disorder due to null mutations in the RAG1 gene resulting in less than 1% of wild type V(D)J recombination activity. Patients present with neonatal onset of life-threatening, severe, recurrent infections by opportunistic fungal, viral and bacterial micro-organisms, as well as skin rashes, chronic diarrhea, failure to thrive and fever. Immunologic observations include profound T- and B-cell lymphopenia, low or absent serum immunoglobulins, and normal natural killer cell counts. As is the case with other types of SCID, RAG1-SCID is fatal in infancy unless immune reconstitution is achieved with hematopoietic stem cell transplantation (HSCT).

On November 10, 2021 Pharos iBio reported its PHI-501, a next-generation anticancer drug for acute myeloid leukemia (AML), has won orphan drug designation from the U.S. Food and Drug Administration (FDA) (Press release, Pharos iBio, NOV 10, 2021, View Source [SID1234595286]).

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It was the U.S. regulator’s second orphan drug designation of the Korean company’s product. FDA granted similar status to Pharos iBio’s main pipeline, PHI-101, a next-generation FMS-like tyrosine kinase 3 (FLT3) inhibitor for AML, in 2019.

PHI-501 is the first targeted anticancer therapeutics against neuroblastoma-RAS (NRAS) mutation using a more effective method for inhibition using synthetic lethality.

NRAS is a protein that plays a significant role in cell differentiation, proliferation, and survival in acute myeloid leukemia. However, NRAS mutants continuously send signals for cell growth which also leads to cancer growth.

According to Decision Resources Group, a global health industry research firm, AML is a rare disease that shows increased occurrence in the older populations above 65. It is particularly prevalent in the U.S. and Europe. The group expected the global market for AML treatments to reach $2.5 billion by 2025 with a 15 percent annual growth.

Pharos iBio holds eight new drug pipelines, including PHI-101, and originally built big data and AI-based platform technology.

Through open innovations, the company plans to promote joint research and development and technology transfer with global pharmaceutical companies and overseas organizations.

"We will benefit from various incentives, including shortened review period for clinical approval and commercialization, reduced application fee with tax exemption, and a seven-year marketing exclusivity," said Pharos iBio CDO Han Hye-jung, former principal scientist at Roche Sequencing Solutions. "We will speed up the clinical trials of PHI-501 to enter the global market."

The company has recently built a synthesis and bio laboratory at its headquarters in Anyang, Gyeonggi Province, establishing an infrastructure to discover new drug candidates independently.

Pharos iBio received approval for the first phase 1 clinical trial of PHI-101 in Korea and continued to strengthen its ability to develop new drugs for rare and incurable diseases.

On November 10, 2021 CureVac N.V. (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid ("mRNA"), reported promising data from the completed dose-escalation part of the Phase 1 clinical trial of CV8102, the company’s lead oncology candidate (Press release, CureVac, NOV 10, 2021, View Source [SID1234595052]). The data support the hypothesis that local injection of the RNA immuno-modulator into a single tumor lesion is able to induce a systemic response leading to immune attack against both injected and non-injected tumors. Extensive analysis of immune cell activation shows efficient stimulation of the immune system characterized by the induction of interferon alpha and interferon gamma signaling pathways. Serial tumor biopsies from individual patients demonstrated increased infiltration of tumor-fighting T cells in the microenvironment of injected as well as non-injected tumors. The study focuses on patients with advanced cutaneous melanoma, adenoid cystic carcinoma and squamous cell carcinoma of the skin or head and neck, treated with CV8102 alone and in combination with anti-PD-1 antibodies. The data are being presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Conference, held in Washington, D.C., and virtually from November 10–14, 2021.

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"The preliminary data from the Phase 1 dose escalation part of this study allow a much deeper understanding of the promising biologic effects of CV8102 observed in several patients," said Dr. Klaus Edvardsen, Chief Development Officer at CureVac. "CV8102 is designed to mimic a viral infection of the injected tumor. This potentially leads to a broad activation of tumor-specific T cells, which can kill tumor cells at the injected but also at distant sites. We expect that the data will be supplemented by upcoming results of the expansion study, which will provide further insight into which patients are more likely to experience a clinical response to CV8102."

An expansion part of the Phase 1 study, initiated in February and fully recruited in October 2021, aims to confirm the safety, tolerability and efficacy of CV8102 at the recommended 600μg dose in patients with advanced melanoma. The study involves 40 trial participants, with 10 in the single-agent cohort and 30 in the combination cohort. Data from the expansion part of the study is expected in the second half of 2022.

The dose-escalation part of the study included a total of 58 patients, 33 of which were treated in the in the single-agent cohort and 25 in the combination cohort. Data presented in September at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) conference found that as of the cutoff date of June 21, 2021, in the single-agent CV8102 dose-escalation cohort, one patient with a complete response and two patients with a partial response were observed. In addition, 12 patients experienced stable disease. In the PD-1 combination dose-escalation cohort, one PD-1 refractory melanoma patient experienced a partial response while three patients experienced stable disease.

About CV8102 and the Phase 1 Clinical Trial

CV8102 is a single-stranded non-coding RNA optimized to maximize activation of cellular receptors that normally detect viral pathogens entering the cells, such as toll-like receptors 7 and 8 (TLR7/8), and retinoic acid inducible gene I (RIG-I), mimicking a viral infection of the tumor. CV8102 is designed to recruit and activate antigen-presenting cells at the site of injection to present tumor antigens released from tumor cells to T cells in the draining lymph node. This potentially leads to activation of tumor-specific T cells, which can kill tumor cells at the injected site, but also at distant non-injected tumor lesions or metastases.

The Phase 1, open-label, dose escalation and expansion study of CV8102 is fully recruited and includes patients with advanced melanoma, cutaneous squamous cell carcinoma, squamous cell carcinoma of head and neck or adenoid cystic carcinoma. The primary objective of the study is to assess safety and tolerability of CV8102.The dose escalation part tests escalating doses of single-agent CV8102 and CV8102 in combination with licensed anti-PD-1 antibodies in the range of 25-900µg. The expansion part of the study focuses on patients with advanced melanoma treated with a recommended dose of 600µg.