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.)
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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.
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●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 Diffusion Pharmaceuticals Inc. (NASDAQ: DFFN) ("Diffusion" or the "Company"), a biopharmaceutical company developing novel therapies that enhance the body’s ability to deliver oxygen to areas where it is needed most, reported financial results for the third quarter of 2021 and provided a business update (Press release, Diffusion Pharmaceuticals, NOV 10, 2021, View Source [SID1234595760]).

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"We believe this is an exciting time for Diffusion Pharmaceuticals. The data we have obtained over the last year from our TCOM and COVID-19 studies have enhanced our understanding of TSC dosing and its mechanism of action, which we feel provides support for the broad potential use of TSC as a treatment for conditions complicated by hypoxia. As the next step in our efforts to realize TSC’s broad potential, we have chosen to target the treatment of hypoxic solid tumors as a first indication," said Robert Cobuzzi, Jr. Ph.D., President and CEO of Diffusion. Dr. Cobuzzi continued, "We believe targeting hypoxic solid tumors is right for TSC given the significant unmet medical need, the compelling preclinical and clinical data accumulated to date, and the current, intravenous formulation of TSC. As a prelude to launching the first clinical study in the program, we plan to obtain input from the U.S. Food and Drug Administration ("FDA") on its design in early 2022, and our study start date will be dependent upon FDA feedback and the availability of clinical drug supply. In the meantime, we will continue to execute on the final two Oxygenation Trials. On that, I am happy to say we plan to dose the first subject in the Altitude Trial within the next couple weeks, and in parallel we are working to initiate the ILD-DLCO Trial."

TSC Development Plans for 2021 and 2022

The Oxygenation Trials

In June 2021, Diffusion reported a positive trend in oxygenation from its Phase 1b TCOM Trial evaluating the effect of TSC versus placebo on peripheral tissue oxygenation in healthy normal volunteers using transcutaneous oxygen measurements. The data obtained from the TCOM Trial have been used to guide dose selection in the Company’s two additional Oxygenation Trials–the Altitude Trial and the ILD-DLCO Trial.

Altitude Trial: This trial will be a double-blind, randomized, placebo-controlled study to evaluate the effects of TSC on maximal oxygen consumption, or VO2, and partial pressure of blood oxygen, or PaO2, in normal healthy volunteers subjected to incremental levels of physical exertion while exposed to hypoxic and hypobaric conditions (i.e., simulated altitude). The study is designed to evaluate the effect of TSC versus placebo on maximal oxygen consumption and partial pressure of blood oxygen. The Company expects dosing of the first subject in the Altitude Trial in November 2021 and expects to complete the study in late December 2021 or early January 2022. The Company anticipates reporting topline results from the Altitude Trial within two months of study completion.

ILD – DLCO Trial: This trial will be a double-blind, randomized, placebo-controlled study which will evaluate the effects of TSC on the diffusion of carbon monoxide through the lungs ("DLCO") in patients with previously diagnosed interstitial lung disease who have a baseline DLCO test result that is abnormal. DLCO will act as a surrogate measure of oxygen transfer efficiency, or uptake, from the alveoli of the lungs, through the plasma, and onto hemoglobin within red blood cells. The study will be statistically powered to evaluate the difference in effect of TSC versus placebo on improvement in DLCO as well as in a standard six-minute walk test. Diffusion anticipates initiating the ILD-DLCO Trial late in the fourth quarter of 2021 and completing the trial in the first quarter of 2022, with topline results reported within two months of study completion.

In addition, with the clearance of the Investigational New Drug application ("IND") to support the ILD-DLCO Trial from the Pulmonary, Allergy, and Critical Care division of the FDA received during the third quarter, Diffusion now has open INDs for TSC with four FDA divisions: Pulmonary, Allergy, and Critical Care; Cardiology and Nephrology, Neurology and Oncology.

The Company believes these Oxygenation Trials remain integral to the overall development plan for TSC, as they are intended to provide further information regarding TSC’s mechanism of action and dose-response characteristics, as well as to support what the Company believes is the broad therapeutic potential of TSC to treat a variety of conditions complicated by hypoxia. More specifically, the Altitude Trial is designed to provide information on TSC’s effects on oxygen consumption, and the ILD-DLCO Trial is designed to evaluate the effects of TSC on the uptake of oxygen through the lungs.

Using TSC to Treat Hypoxic Solid Tumors

While the Company intends to continue developing data to support TSC’s broad potential uses, it has announced that its near-term focus will be the design and execution of a clinical program to support the use of intravenously administered TSC as a treatment for hypoxic solid tumors.

"Solid tumors comprise approximately 90% of all adult cancers, and according to the American Cancer Society, roughly 1.9 million new cancer cases will be diagnosed in the U.S. alone during 2021. Hypoxia is a common complicating factor in nearly all solid tumors, directly contributing to treatment resistance and metastatic potential. Tumor hypoxia has been studied for decades and continues to be an area of unmet need that negatively influences treatment outcomes independent of modality," said Chris Galloway, M.D., Chief Medical Officer of Diffusion. Dr. Galloway went on to state, "We believe TSC’s unique mechanism of action along with its safety profile has the potential to improve treatment success of solid tumors coincident with standard of care therapy. Diffusion has existing pre-clinical and clinical evidence of TSC’s potential positive effects in solid tumors, and now further informative exposure-response data from recently completed studies like the Oxygenation Trials and our COVID-19 trial. Building upon this we are actively working to design a targeted development plan in multiple solid tumor types and plan to submit a briefing document to the FDA in early 2022. In parallel, data from the upcoming Altitude and ILD-DLCO Trials will be used to refine and enhance our understanding of TSC’s dose and effects that conceivably translate into a multitude of oncology and non-oncology indications."

3Q21 Financial Results

Research and development expenses in the third quarter were $2.1 million compared to expenses of $3.1 million in the prior year period, a decrease of $1.0 million. This decrease was attributable to the completion of the Company’s clinical trial evaluating TSC in COVID-19 patients in February and the wind-down of the Company’s glioblastoma multiforme and stroke trials, and partially offset by increased headcount and costs related to the startup of the Altitude and ILD-DLCO Trials.

General and administrative expenses were $1.9 million during the third quarter of 2021 versus $2.1 million in the comparable quarter last year. The decrease compared to the prior year period was primarily attributable to executive separation payments in the prior year period partially offset by increased salaries, wages, stock-based compensation, and professional fees related to increased headcount in 2021.

The Company recognized a non-recurring, non-cash asset impairment charge of $8.6 million during the third quarter of 2021 versus $0.0 in the comparable quarter last year. The charge was related to the full impairment of the in-process research and development asset associated with the Company’s DFN-529 product candidate, which was acquired in January 2016 in connection with the reverse merger of Diffusion Pharmaceuticals LLC and RestorGenex Corporation.

The Company’s third quarter 2021 operating loss was $12.6 million as compared with an operating loss of $5.2 million in the third quarter of 2020, with the increase primarily attributable to the $8.6 million non-cash asset impairment charge described above. Excluding the asset impairment charge, the Company’s operating loss decreased by $1.3 million.

As of Sept 30, 2021, Diffusion had cash and cash equivalents of approximately $40.3 million as compared to $18.5 million as of December 31, 2020. The increase was primarily attributable to the proceeds of the Company’s public offering of common stock in February 2021. Diffusion estimates that it has sufficient cash to fund operations and capital expenditures through 2023.