On November 10, 2021 Decibel Therapeutics (Nasdaq: DBTX), a clinical-stage biotechnology company dedicated to discovering and developing transformative treatments to restore and improve hearing and balance, reported financial results for the third quarter ended September 30, 2021 and provided a corporate update (Press release, Decibel Therapeutics, NOV 10, 2021, View Source [SID1234595132]).

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"Decibel continues to work towards bringing transformative treatments to patients with hearing and balance disorders as we move to the end of a successful 2021 and look forward to 2022. We remain on track to initiate a Phase 1/2 clinical trial of DB-OTO in pediatric patients in 2022 and report the results of an interim analysis of our Phase 1b clinical trial of DB-020 in patients receiving cisplatin chemotherapy in the first half of 2022," said Laurence Reid, Ph.D., Chief Executive Officer of Decibel. "We are incredibly pleased to have received Orphan Drug and Rare Pediatric Disease designations for DB-OTO, reiterating the importance of our approach to gene therapies for congenital, monogenic hearing loss. Beyond DB-OTO, we have continued to leverage our precision gene therapy platform to advance our GJB2, stereocilin and regeneration gene therapy programs."

Gene Therapies for Congenital, Monogenic Hearing Loss

Received Orphan Drug and Rare Pediatric Disease Designations for DB-OTO: In September 2021, Decibel announced that the U.S. Food and Drug Administration (FDA) granted both Orphan Drug Designation and Rare Pediatric Disease Designation for DB-OTO for the treatment of otoferlin-related congenital hearing loss.
On Track to Achieve DB-OTO Key Milestones in 2022: Decibel expects to submit an investigational new drug application (IND) with the FDA and/or a Clinical Trial Application (CTA) in Europe for DB-OTO and initiate a Phase 1/2 clinical trial of DB-OTO for pediatric patients with congenital hearing loss due to an otoferlin deficiency in 2022.
Announces AAV.104 Gene Therapy Program for Restoration of Hearing in Patients with Congenital Hearing Impairment Due to Recessive Mutations in the Stereocilin (STRC) Gene: AAV.104 aims to restore hearing to individuals with a STRC deficiency, the second most common cause of autosomal recessive, non-syndromic, congenital hearing loss. The Company estimates that the prevalence of individuals with this form of hearing loss in the United States and the major markets in Europe is approximately 70,000. STRC is a large, extracellular, structural protein expressed in outer hair cells of the cochlea. Functional outer hair cells amplify sound within the ear, a process required for normal hearing sensitivity and frequency selectivity. Despite the absence of the STRC protein and observed hearing loss in patients carrying STRC mutations, third-party research has shown that the outer hair cells remain intact and viable for gene therapy. AAV.104 is designed to express STRC selectively in outer hair cells, thus providing STRC specifically in its natural cellular location, a strategy that has the potential to restore expression of the protein and hearing. Decibel is working in collaboration with Regeneron to develop AAV.104 and plans to share preclinical data on this program at an upcoming scientific meeting.
Gene Therapies for Hair Cell Regeneration

On Track to Announce AAV.201 Program Target: Decibel continues to advance AAV.201, its gene therapy program for regeneration of hair cells in the vestibule for the treatment of bilateral vestibulopathy (BVP). Decibel plans to announce the program target(s) for AAV.201 in 2022.
Otoprotection Therapeutic

On Track to Report Interim Results from Phase 1b Proof-of-Concept Trial of DB-020 for the Treatment of Cisplatin-Induced Hearing Loss: Decibel expects to report interim results from the ongoing Phase 1b clinical trial of DB-020 in patients with cisplatin-induced hearing loss, a serious and debilitating condition for which there are no approved therapies, in the first half of 2022. Cisplatin, a commonly used chemotherapy agent, is known to cause hearing loss, tinnitus and speech recognition difficulty. DB-020 comprises a proprietary formulation of sodium thiosulfate which has been optimized for delivery to the ear. By locally disabling cisplatin in the cochlea, DB-020 is designed to protect hearing without interfering with cisplatin’s anti-cancer activity.
Granted Key U.S. Patent Covering DB-020 Formulation: In July 2021, the United States Patent and Trademark Office (USPTO) issued U.S. Patent No. 11,071,751, "Hypertonic pharmaceutical compositions containing an anti-platinum chemoprotectant agent," a foundational patent and component of Decibel’s DB-020 intellectual property portfolio.
Research Highlights:

Announced Foundational Study of Noise-Related Inner Ear Damage: In September 2021, Decibel announced the publication of new findings in Cell Reports from a study on noise-related inner ear damage conducted in collaboration with the University of Maryland School of Medicine and the Karolinska Institute. This study demonstrates how Decibel’s platform is built to provide a molecular characterization of the cells of the inner ear to enable the identification of therapeutics that counter the underlying molecular pathology of noise-induced hearing loss in the future.
Third Quarter 2021 Financial Results:

Cash Position: As of September 30, 2021, cash, cash equivalents and available-for-sale securities were $172.4 million.
Research and Development Expenses: Research and development expenses were $9.0 million for the third quarter of 2021, compared to $4.7 million for the third quarter of 2020. The increase in research and development expenses for the third quarter of 2021 was driven primarily by an increase in costs associated with IND/CTA enabling activities for DB-OTO.
General and Administrative Expenses: General and administrative expenses were $5.7 million for the third quarter of 2021, compared to $2.4 million for the same period in 2020. The increase in general and administrative expenses for the third quarter of 2021 was primarily attributable to increases in professional fees, personnel costs and directors’ and officers’ insurance costs incurred as a result of becoming a public company.
Financial Guidance:

Based on its current operating and development plans, Decibel believes that its existing cash, cash equivalents and available-for-sale securities will fund its pipeline programs and operating expenses into 2024.

On November 10, 2021 Nuvation Bio Inc. (NYSE: NUVB), a biopharmaceutical company tackling some of the greatest unmet needs in oncology by developing differentiated and novel therapeutic candidates, reported financial results for the third quarter ended September 30, 2021, and provided a business update (Press release, Nuvation Bio, NOV 10, 2021, View Source [SID1234595148]).

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"In the third quarter, Nuvation Bio continued to advance our lead cyclin-dependent kinase (CDK) 2/4/6 inhibitor program, with enrollment progressing in the ongoing Phase 1/2 study of NUV-422 for the treatment of adult patients with recurrent glioblastoma, malignant gliomas, hormone receptor-positive breast cancer and metastatic castration-resistant prostate cancer. We remain on track to report top-line data from the Phase 1 portion of the study in 2022," said David Hung, M.D., founder and chief executive officer of Nuvation Bio. "Additionally, we remain well capitalized to advance our full pipeline of novel oncology therapeutic candidates for difficult-to-treat cancers and look forward to providing clinical development updates."

Recent Business Highlights

Enrollment ongoing in Phase 1/2 multiple expansion cohort study of NUV-422. During the third quarter of 2021, Nuvation Bio continued to enroll patients in the Phase 1/2 study of NUV-422, a CDK 2/4/6 inhibitor. The Company submitted a protocol amendment to the U.S. Food and Drug Administration (FDA) in the second quarter, expanding the study to include additional cohorts for patients with recurrent glioblastoma, hormone receptor-positive metastatic breast cancer (with and without brain metastases) and metastatic castration-resistant prostate cancer. Enrollment is ongoing and data from the Phase 1 portion of the study is expected in 2022.
Second Quarter Financial Results

As of September 30, 2021, Nuvation Bio had cash, cash equivalents and marketable securities of $791.8 million.

For the three months ended September 30, 2021, research and development expenses were $17.1 million, compared to $8.6 million for the three months ended September 30, 2020. The increase was primarily due to a $5.3 million increase in third-party costs related to research services and manufacturing to advance our current preclinical programs and Phase 1/2 clinical trial, as well as a $3.2 million increase in personnel-related costs driven by an increase in headcount and stock-based compensation.

For the three months ended September 30, 2021, general and administrative expenses were $5.7 million, compared to $2.9 million for the three months ended September 30, 2020. The increase was primarily due to a $1.9 million increase in personnel-related costs driven by an increase in headcount and stock-based compensation, a $1.1 million increase in insurance, a $0.3 million increase in other miscellaneous expenses offset by a $0.4 million decrease in professional fees and a $0.1 million decrease in legal fees.

For the three months ended September 30, 2021, Nuvation Bio reported a net loss of $22.0 million, or $(0.11) per share. This compares to a net loss of $11.0 million, or $(0.12) per share, for the comparable period in 2020.

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).