On November 10, 2021 Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage precision oncology company developing targeted drugs to inhibit frontier targets that drive and sustain RAS-addicted cancers, reported its financial results for the third quarter and nine months ended September 30, 2021, and provided a corporate update (Press release, Revolution Medicines, NOV 10, 2021, View Source [SID1234595098]).

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"During the third quarter, the company’s unique capabilities and continuing momentum with our innovative RAS(ON) Inhibitors and RAS Companion Inhibitors strengthened Revolution Medicines’ leadership position in the quest to successfully treat RAS-addicted cancers. In our RAS(ON) Inhibitor portfolio, development candidates targeting KRASG12C (RMC-6291) and RASMULTI (RMC-6236) have shown compelling features and continue to advance toward the clinic. Exciting mutant-selective inhibitors of KRASG13C and KRASG12D have also emerged from our RAS(ON) drug discovery platform, and we expect to select another development candidate by year end," said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines.

"We have expanded the evaluation of our SHP2 inhibitor, RMC-4630, in combination regimens with direct inhibitors of RAS. In particular, the company recently began recruiting patients in our RMC-4630-03 study under our global partnership with Sanofi and in collaboration with Amgen. This study is intended to further evaluate RMC-4630 and Lumakras in the treatment of lung cancer as a complement to the ongoing CodeBreaK 101c study of these compounds. In addition, we are gratified that Sanofi plans to sponsor a study of RMC-4630 in combination with Mirati’s KRASG12C inhibitor, adagrasib, also under our partnership."

RAS(ON) Inhibitors – Revolution Medicines continues to build on its innovative RAS(ON) Inhibitor platform, producing an expansive collection of tri-complex inhibitors targeting diverse oncogenic RAS variants through highly differentiated chemical and pharmacologic profiles.

RMC-6291 (KRASG12C) – RMC-6291 is a first-in-class, potent, oral and selective tri-complex inhibitor of KRASG12C(ON) with a differentiated preclinical profile designed to address persistent unmet needs for patients with cancers driven by KRASG12C.
The company recently reported data 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) demonstrating superior outcomes with orally administered RMC-6291 as compared to adagrasib in preclinical models of KRASG12C non-small cell lung cancer (NSCLC). In a head-to-head mouse clinical trial of 19 xenograft models, RMC-6291 demonstrated robust anti-tumor activity characterized by a 68% objective response rate, as compared to 42% for adagrasib in the same models. The company believes these findings support the potential for RMC-6291 as a best-in-class KRASG12C inhibitor.
The company remains on track to submit an Investigational New Drug application (IND) for RMC-6291 in the first half of 2022.
RMC-6236 (RASMULTI) – RMC-6236 is a first-in-class, potent, oral RAS-selective tri-complex, RASMULTI(ON) inhibitor designed to treat cancers driven by a variety of KRAS mutations, including those that have emerged in patients following treatment with KRASG12C(OFF) inhibitors.
The company reported data at the AACR (Free AACR Whitepaper)-NCI-EORTC Conference demonstrating RMC-6236’s ability to induce significant regressions of NSCLC, pancreatic cancer and colorectal cancer (CRC) xenograft models driven by KRASG12V, KRASG12D, KRASG12C or KRASG12R. These findings add to the growing body of evidence that the company believes supports the potential of RMC-6236 as a first targeted therapy for treating many cancers for which no targeted treatment is currently available.
The company presented an expanded dataset at the Gastrointestinal Cancer Drug Development Summit demonstrating the ability of both RMC-6236 and RMC-6291 to drive tumor regressions in xenograft models of RAS-mutant CRC. The company believes these findings provide additional support for the potential of RAS(ON) inhibitors to deliver clinical benefit to patients with CRC.
Also during the AACR (Free AACR Whitepaper)-NCI-EORTC Conference, the company presented preclinical data from a combination study evaluating RMC-6236 with a PD-1 inhibitor. Results from this study demonstrated that RMC-6236 alone induces anti-tumor immunity in vivo, and also exhibits additive anti-tumor benefit with checkpoint inhibition as indicated by complete and durable responses.
The company remains on track to submit an IND for RMC-6236 in the first half of 2022.
Continued expansion of other RAS(ON) Inhibitor programs – Revolution Medicines continues to progress its growing portfolio of orally bioavailable, mutant-selective RAS(ON) Inhibitors designed to target RAS variants driving RAS-addicted cancers that are unserved by targeted drugs.
The company reported data at the AACR (Free AACR Whitepaper)-NCI-EORTC Conference showing the capacity of compounds from both its KRASG13C and KRASG12D programs to covalently and selectively modify their respective targets, the first compounds described with these properties. Covalent modification of KRASG12D was also demonstrated in vivo in a tumor xenograft model of KRASG12D-driven pancreatic cancer, with tumor regressions achieved following repeat oral dosing.
The company remains on track to nominate a third development candidate from its RAS(ON) inhibitor portfolio in 2021.
RAS Companion Inhibitors – Revolution Medicines continues to advance and expand multiple clinical studies of its RAS Companion Inhibitors designed to provide maximum clinical benefit in RAS-addicted cancers.

RMC-4630 (SHP2 Inhibitor) – RMC-4630, a potent, oral, selective inhibitor of the SHP2 protein, is being advanced in partnership with, and is primarily funded by, Sanofi.
RMC-4630 and KRASG12C inhibitor Lumakras (sotorasib)
Amgen’s CodeBreaK 101c study continues evaluating RMC-4630 in combination with sotorasib across multiple cancer types. To date this combination has demonstrated acceptable tolerability.
The company is actively recruiting patients for its global Phase 2 clinical trial evaluating the combination of RMC-4630 and sotorasib in patients with advanced NSCLC bearing the KRASG12C mutation. Revolution Medicines is sponsoring the RMC-4630-03 study under its global partnership with Sanofi and conducting the trial in collaboration with Amgen. The RMC-4630-03 study evaluating the combination in NSCLC patients is a complement to Amgen’s ongoing CodeBreaK 101c study exploring this combination across multiple cancer types. The company expects to have preliminary findings from the RMC-4603-03 study in the second half of 2022.
RMC-4630 and KRASG12C inhibitor adagrasib
Sanofi, the company’s global SHP2 development and commercialization partner, plans to sponsor a combination study under its global SHP2 partnership with the company evaluating RMC-4630 (also known as SAR442720) in combination with Mirati’s KRASG12C inhibitor, adagrasib. This study expands the evaluation of the potential benefit of adding RMC-4630 in this class of RAS inhibitors.
RMC-4630 and PD-1 inhibitor pembrolizumab (Keytruda)
The TCD16210 study sponsored by Sanofi continues evaluating RMC-4630 in combination with pembrolizumab, a PD-1 inhibitor. Sanofi is planning an expansion cohort with this combination in front-line PD-L1+ NSCLC.
RMC-5552 (mTORC1/4EBP1 Inhibitor) – RMC-5552 is a potent, selective bi-steric inhibitor of mTORC1 that suppresses phosphorylation and inactivation of 4EBP1.
Enrollment and dosing are underway in a Phase 1 monotherapy dose-escalation study. The company continues to expect initial safety, pharmacokinetic and single agent activity data in 2022.
The company intends to evaluate RMC-5552 in combination with RAS inhibitors for the treatment of tumors driven by co-occurring RAS mutations and genomic activation of the mTORC1 pathway.
RMC-5845 (SOS1 Inhibitor) – RMC-5845 is a potent, selective, oral inhibitor of SOS1, a major switch in the cycling of RAS(OFF) to RAS(ON).
The company expects RMC-5845 to be IND-ready by the end of 2021.
Third Quarter 2021 Financial Highlights

Cash Position: Cash, cash equivalents and marketable securities were $608.7 million as of September 30, 2021, compared to $440.7 million as of December 31, 2020. The increase was primarily due to proceeds from the company’s public equity offering in February 2021.

Revenue: Total revenue consists of revenue from the company’s collaboration agreement with Sanofi. During the third quarter of 2021, the company recorded a non-cash, non-recurring GAAP accounting adjustment that reduced collaboration revenue by $8.5 million. This non-cash revenue adjustment relates to the addition of the RMC-4630-03 study to the RMC-4630 development plan, and deprioritization of the RMC-4630-02 study. As a result of these development plan events, the company revised its estimate of the accounting transaction price and percentage of completion of work performed to date under its agreement with Sanofi, which resulted in a cumulative catch-up adjustment to collaboration revenue in this quarter. Total revenue, including the non-cash revenue adjustment, was $1.1 million for the quarter ended September 30, 2021, compared to $12.7 million for the quarter ended September 30, 2020. The decrease was primarily due to the non-cash revenue adjustment and lower reimbursed manufacturing costs.

R&D Expenses: Research and development expenses were $46.5 million for the quarter ended September 30, 2021, compared to $34.9 million for the quarter ended September 30, 2020. The increase was primarily due to an increase in research expenses associated with the company’s pre-clinical research portfolio, an increase in personnel-related expenses related to additional headcount, and an increase in stock-based compensation.

G&A Expenses: General and administrative expenses were $7.8 million for the quarter ended September 30, 2021, compared to $5.3 million for the quarter ended September 30, 2020. The increase was primarily due to an increase in stock-based compensation, an increase in personnel-related expenses related to additional headcount, and higher legal and accounting fees.

Net Loss: Net loss was $52.9 million for the quarter ended September 30, 2021, compared to a net loss of $27.2 million for the quarter ended September 30, 2020.

2021 Financial Guidance

Revolution Medicines continues to expect full year 2021 GAAP net loss to be between $170 million and $190 million, which includes estimated non-cash stock-based compensation expense of approximately $20 million.

Conference Call

Revolution Medicines will host a conference call and webcast this afternoon, November 10, 2021, at 4:30 PM Eastern (1:30 PM Pacific).

To listen to the conference call, please dial (833) 423-0425 or (918) 922-3069, provide conference ID: 9757524 and request the Revolution Medicines conference call. To listen to the live webcast, or access the archived webcast, please visit: View Source Following the live webcast, a replay will be available on the Company’s website for at least 14 days.

On November 10, 2021 Synlogic, Inc. (Nasdaq: SYBX), a clinical-stage company bringing the transformative potential of synthetic biology to medicine, reported financial results for the third quarter ended September 30, 2021 and provided an update on clinical programs (Press release, Synlogic, NOV 10, 2021, View Source [SID1234595114]).

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"We are very pleased to be moving our Phenylketonuria (PKU) program into late-phase clinical development with the goal of bringing forward a clinically meaningful and differentiated medicine to the PKU community. The positive interim analysis from the Phase 2 SynPheny-1 study gives us confidence as we prepare to launch a Phase 3 program in PKU in 2022," said Aoife Brennan, M.B. Ch.B., Synlogic President and Chief Executive Officer. "We continue to advance oral metabolic programs in other areas of high unmet need as well as drive our research engine forward, including achieving an important early milestone in our IBD collaboration with Roche. The Synthetic Biotic platform is proving to be a potent and rapid source of novel therapeutic candidates."

Recent Portfolio Highlights

Metabolic Portfolio

Phenylketonuria (PKU): Proof of concept of SYNB1618 achieved in an interim analysis. Full study results of both SYNB1618 and SYNB1934, and advancement of Phase 3 program, expected in 2022.

In September, the Company reported SYNB1618 demonstrated proof of concept in PKU patients, with a clinically meaningful and statistically significant reduction of plasma phenylalanine (Phe) levels in an interim analysis of the Phase 2 SynPheny-1 study.
SYNB1934, an optimized strain of SYNB1618, further demonstrated a two-fold increase in biomarkers of Phe metabolism compared to SYNB1618 in a head-to-head healthy volunteer study.
The Phase 2 SynPheny-1 study has been amended to incorporate SYNB1934, with results expected in the first half of 2022.
Synlogic is preparing to start a Phase 3 program with the preferred strain based on the SynPheny-1 study data in phenylketonuria (PKU) in 2022.
Further data on the Synlogic PKU program will be presented at the 14th International Congress of Inborn Errors of Metabolism (ICIEM) meeting to be held in Sydney, Australia and virtually on November 21 – 24, 2021.
Enteric Hyperoxaluria: Proof of concept data of SYNB8802 anticipated in 2022.

In April, the Company reported that SYNB8802 demonstrated proof of mechanism in Part A of an ongoing Phase 1 study, with robust and dose-dependent evidence of urinary oxalate lowering in healthy volunteers given a high oxalate diet.
Part B of the study is continuing to evaluate of SYNB8802 in patients with enteric hyperoxaluria secondary to Roux-en-Y gastric bypass surgery, with data expected next year.
Further data on SYNB8802 and enteric hyperoxaluria were presented at the American Urological Association 2021 Annual Meeting and the American Society of Nephrology Kidney Week 2021, including real-world evidence demonstrating a relationship between higher urinary oxalate levels and increased incidence of chronic kidney disease.
Homocystinuria (HCU): Synlogic and Ginkgo announced that SYNB1353 for the treatment of homocystinuria has been advanced into IND-enabling studies, with entry into the clinic expected in 2022.

SYNB1353 was developed using Synlogic’s Synthetic Biotic platform incorporating components of Ginkgo Bioworks’ codebase. Synlogic holds worldwide development and commercialization rights.
Further data on this program will be presented at the 14th International Congress of Inborn Errors of Metabolism (ICIEM) meeting to be held in Sydney, Australia and virtually on November 21 – 24, 2021.
Synlogic and Ginkgo continue to advance their long-term strategic platform collaboration with multiple undisclosed metabolic and immunology programs now in preclinical development.
Immunomodulation Portfolio

Achievement of preclinical milestone in research collaboration with Roche

In June 2021, Synlogic and Roche entered into a research collaboration agreement for the discovery of a novel Synthetic Biotic medicine for the treatment of inflammatory bowel disease (IBD), addressing an undisclosed novel target in IBD.
During the third quarter, Synlogic achieved a prespecified research milestone and earned the first milestone payment due under the terms of the collaboration.
Phase 1 study of SYNB1891 in combination with PD-L1 checkpoint inhibitor patients with advanced solid tumors or lymphoma has completed enrollment.

Results will be presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2021 annual meeting to be held in Washington, D.C. and virtually on November 10 – 14, 2021.
No further studies are planned for SYNB1891 at this time.
Corporate Updates

Synlogic strengthens balance sheet and builds leadership team

In September, Synlogic completed an underwritten public offering of 17.3 million shares, resulting in net proceeds to Synlogic of approximately $48.4 million.
Synlogic appointed Molly Harper to the newly created position of Chief Business Officer. Ms. Harper will provide strategic leadership to the commercial, corporate development and business development functions, and lead the planning and commercialization of Synlogic’s growing pipeline.
Third Quarter 2021 Financial Results

As of September 30, 2021, Synlogic had cash, cash equivalents, and short-term investments of $150.1 million.

For the three months ended September 30, 2021, Synlogic reported a consolidated net loss of $16.0 million, or $0.29 per share, compared to a consolidated net loss of $13.2 million, or $0.36 per share, for the corresponding period in 2020.

Research and development expenses were $13.4 million for the three months ended September 30, 2021 compared to $10.5 million for the corresponding period in 2020.

General and administrative expenses for the three months ended September 30, 2021 were $3.6 million compared to $3.0 million for the corresponding period in 2020.

Revenue was $0.9 million for the three months ended September 30, 2021. There was no revenue for the three months ended September 30, 2020. Revenue in 2021 was associated with the ongoing research collaboration with Roche for the discovery of a novel Synthetic Biotic medicine for the treatment of IBD.

Financial Outlook

Based upon its current operating plan and balance sheet as of September 30, 2021 Synlogic expects to have sufficient cash to be able to fund operations into 2024.

Conference Call & Webcast Information

Synlogic will host a conference call and live webcast at 8:30 a.m. ET today, Wednesday, November 10, 2021. To access the live webcast, please visit the "Event Calendar" page within the Investors and Media section of the Synlogic website. Investors may listen to the call by dialing +1 (844) 815-2882 from locations in the United States or +1 (213) 660-0926 from outside the United States. The conference ID number is 5450919. A replay will be available for 30 days on the Investors and Media section of the Synlogic website.

On November 10, 2021 Autolus Therapeutics plc (Nasdaq: AUTL), a clinical-stage biopharmaceutical company developing next-generation programmed T cell therapies, reported the publication of an article in Nature Scientific Reports describing a controllable CAR T cell system (TetCAR), designed to reversibly dampen the activity of the programmed T cells by the administration of the licensed and widely available antibiotics tetracycline and minocycline (Press release, Autolus, NOV 10, 2021, View Source [SID1234595131]).1

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Management of toxicities is a critical step in the successful application of programmed cell therapies. TetCAR is one of a number of approaches developed at Autolus that use a pharmacological agent to selectively control or eliminate cell therapies in the event a patient experiences severe adverse side effects from the treatment.

Safety switches, like Autolus’ Rituxumab and Rapamycin controlled systems (RQR82 and RapaCasp93), are designed to selectively eliminate a programmed cell therapy following administration of a pharmacological agent, whilst controllable systems, like the TetCAR approach described in this publication, are designed to allow the activity of a CAR T cell therapy to be dialed down following administration of a pharmacological agent to a patient and then subsequently restored on clearance of the pharmacological agent from the patient.

"While many such systems have been described, most require use of experimental small molecules for control. Our TetCAR, RQR8 and Rapacasp9 approaches, all use licensed and widely available drugs, offering practical application of these systems in the clinic," said Dr. Martin Pule, chief scientific officer of Autolus. "We are excited to highlight this new publication which underscores the strong technology and IP base that we are using to develop the next generation of programmed cell therapies, both in-house and in partnership."

TetCAR: Hotblack A, Kokalaki E, Palton M, Weng-Kit Cheung G, Williams I, Manzoor S, Grothier T, Piapi A, Fiaccadori V, Wawrzyniecka P, Roddy H, Agliardi G, Roddie C, Onuoha S, Thomas S, Cordoba S and Pule M. Tunable control of CAR T cell activity through tetracycline mediated disruption of protein–protein interaction. Nature Scientific Reports, 2021 Nov 9. View Source

RQR8: Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K, Flutter B, Marin V, Marafioti T, Chakraverty R, Linch D, Quezada SA, Peggs KS, Pule M. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014 Aug 21;124(8):1277-87. View Source

RapaCasp9: Maria Stavrou, Brian Philip, Charlotte Traynor-White, Christopher G. Davis, Shimobi Onuoha, Shaun Cordoba, Simon Thomas and Martin Pule. A Rapamycin-Activated Caspase 9-Based Suicide Gene. Molecular Therapy. 2018 May 02; 26(5): 1266-76. View Source
About Autolus Therapeutics plc
Autolus is a clinical-stage biopharmaceutical company developing next-generation, programmed T cell therapies for the treatment of cancer. Using a broad suite of proprietary and modular T cell programming technologies, the company is engineering precisely targeted, controlled and highly active T cell therapies that are designed to better recognize cancer cells, break down their defense mechanisms and eliminate these cells. Autolus has a pipeline of product candidates in development for the treatment of hematological malignancies and solid tumors. For more information please visit www.autolus.com.

About RQR8
Rituximab Safety Switch (RQR8) – The RQR8 safety switch is designed to selectively eliminate the programmed T cells by the administration of the commercially available monoclonal antibody rituximab. Once administered, rituximab binds to the engineered CD20 epitopes on the surface of the T cell and triggers cell death.

About Rapacasp9
Rapamycin Safety Switch (RapaCasp9) – The rapaCasp9 safety switch is designed to selectively eliminate the programmed T cells by the administration of the commercially available drug rapamycin. Once administered, rapamycin heterodimerises caspase 9 via FRB and FKBP to activate a cell death cascade and selectively eliminate the programmed T cells. Rapamycin is a small molecule drug, which we expect will have the benefit of better tissue penetration and may require less time to take effect as compared to a monoclonal antibody-activated safety switch.

About TetCAR
Tetracycline Controllable CAR (TetCAR) – TetCAR is a controllable CAR T cell system designed to reversibly dampen the activity of the programmed T cells by the administration of the commercially available antibiotic tetracycline. Once administered, tetracycline temporarily dislocates the CAR signaling domain from the cancer antigen binding domain leading to deactivation of the T cell therapy. The system is designed to be reversable, and on clearance of tetracycline from the patient, the interaction between the signaling domain and binding domain is restored and the programmed T cells are reactivated. Controllable CAR T cells are intended to be used to manage a patient through a period of severe toxicity whilst also allowing for the subsequent reactivation of programmed T cells and the possibility of persistence and sustained anti-tumor activity.

On November 10, 2021 atrix, Inc. (NASDAQ: PULM), a clinical stage biopharmaceutical company developing innovative inhaled therapies to address serious pulmonary and non-pulmonary disease using its patented iSPERSE technology, reported its third quarter 2021 financial results and provides a business update (Press release, Pulmatrix, NOV 10, 2021, View Source [SID1234595147]).

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"The resolution of our contract dispute with Cipla is an important milestone which will enable the continued development of Pulmazole globally with our valued partners," said Ted Raad, Chief Executive Officer of Pulmatrix. "After our successful FDA Type C Meeting in February, we are excited to resume clinical activities with Pulmazole which has the potential to address the underlying cause of ABPA while avoiding the side effects of oral antifungals and prolonged steroid treatment. In parallel, we are making steady progress across our pipeline with top-line data expected in Q1 2022 from our fully enrolled PUR1800 Phase 1b study and we expect the initiation of a PUR3100 Phase 1study in Q2 2022."

Third Quarter and Recent Highlights:

Pulmazole

On November 8, 2021, we entered into an amendment (the "Amendment") to our development and commercialization agreement with Cipla (the "Cipla Agreement"), which modifies certain provisions of the Cipla Agreement and resolves the current dispute between us and Cipla regarding each party’s respective performance of the Cipla Agreement. Cipla will continue to share 50% of all third-party costs for the development of Pulmazole and will share 40% of our personnel, consulting and overhead costs and will reimburse us for another 10% of such costs upon the timely achievement of development milestones.
As part of the resolution, the Cipla Agreement was amended to grant Cipla exclusive rights to Cipla territories (India, South Africa, Sri Lanka, Nepal, Iran, Yemen, Myanmar and Algeria) in exchange for 2% royalties under certain circumstances. For the Cipla territories, Cipla will be initiating a clinical program and potential commercialization at its own expense. The rest of the global rights will maintain the equal cost sharing related do development and commercialization costs and equal share of free cash flow from future sales of Pulmazole.
Pulmatrix has successfully completed a Type C Meeting with the U.S. Food and Drug Administration (FDA) for the further clinical development of Pulmazole and based on feedback from the Type C Meeting, intends to initiate a Phase 2b clinical study of Pulmazole in allergic bronchopulmonary aspergillosis (ABPA) with registration endpoints in Q1 2023 with topline data expected Q2 2024 which may enable a Phase 3 registration study.
PUR3100

We plan to request a Type C meeting with the FDA to further clarify some of the responses in relation to the overall nonclinical and clinical program. We expect to submit the IND in Q1 2022 and initiate the Phase 1 study in Q2 2022 with top line data expected in Q3 2022. Following the Phase 1 study, we plan to conduct a randomized placebo-controlled Phase 2 study in patients with migraine to assess the safety and effectiveness of 2 PUR3100 doses, in which the selection of the 2 doses has been informed by the initial clinical study. We anticipate that this Phase 2 study will initiate in Q4 2022 and complete in mid 2023.

PUR1800

Enrollment is complete in the ongoing Phase 1b clinical study of PUR1800 in acute exacerbations in COPD (AECOPD). Study endpoints include safety, tolerability, and exploratory biomarkers to demonstrate target engagement and anti-inflammatory effect.
PUR1800 Phase 1b top-line data is expected in Q1 2022.
Financials

As of September 30, 2021, Pulmatrix had $53.5 million in cash and cash equivalents, compared to $31.7 million for the year ended December 31, 2020.

Revenue for the third quarter of 2021 was $1.1 million, compared to $4.4 million for the same period in 2020. The revenue for the third quarter of 2021 was the result of the collaboration and licensing agreements with JJEI.

Research and development expense was $4.0 million in the third quarter of 2021 compared to $3.9 million for the same period in 2020. The increase year–over-year was primarily attributable to increased preclinical and manufacturing costs related to the PUR3100 project partially offset by decreased spend on the PUR1800 program and the Pulmazole Ph2 clinical trial.

General and administrative expense was $1.7 million for the third quarter of 2021 compared to $1.8 million for the same period in 2020. The decrease year–over-year was primarily attributable to decreased employment costs partially offset by increased legal expense.

Net loss was $8.2 million for the third quarter of 2021 compared to a net loss of $10.6 million for the same period of 2020. The $2.4 million decrease in net loss year-over-year resulted from a one- time warrant inducement charge of $9.3 million in 2020 which was partially offset by $3.6 million and $3.3 million that resulted from a goodwill impairment charge and fluctuation in revenue recognition, respectively, in 2021.

On November 10, 2021 TScan Therapeutics, Inc. (Nasdaq: TCRX), a biopharmaceutical company focused on the development of T-cell receptor (TCR) engineered T cell (TCR-T) therapies for the treatment of patients with cancer, reported financial results for the quarter ended September 30, 2021, highlighted recent program progress, and outlined key upcoming expected milestones (Press release, TScan Therapeutics, NOV 10, 2021, View Source [SID1234595217]).

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"Throughout the third quarter of 2021, we’ve continued to execute on our long-term goals of advancing transformational TCR-T therapy candidates and expect to file IND applications for our lead liquid tumor candidates TSC-100 and TSC-101 by the end of the year," said David Southwell, President and Chief Executive Officer. "We look forward to sharing additional details on our liquid tumor program at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. We also made significant progress across our solid tumor pipeline, particularly the advancement of TSC-200 into IND-enabling studies and the launch of a new TCR program based on the discovery of a novel epitope on the validated solid tumor target MAGE-A1."

Third Quarter 2021 and Recent Business Highlights

TScan recently announced that two abstracts related to lead liquid tumor TCR-T therapy candidates TSC-100 and TSC-101 have been accepted for poster presentations at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held from December 11-14, 2021.

During the third quarter, TScan advanced a lead TCR-T therapy candidate for its TSC-200 program for HPV16 into investigational new drug (IND)-enabling activities and plans to submit an IND for this program in the second half of 2022. HPV is a well validated cancer target found in HPV-positive tumors, including many cases of head & neck and cervical cancers. Using its proprietary ReceptorScan and TargetScan platforms, TScan screened over half a billion T cells from a variety of human donors to identify a naturally occurring, ultra-high affinity TCR that recognizes an HLA-A*02:01-restricted epitope derived from the E7 protein of HPV16. Previously, clinical data from the National Cancer Institute (NCI) demonstrated a favorable safety and efficacy profile for an HPV TCR. TScan intends to build on the positive NCI results by developing an enhanced autologous TCR-T therapy using its T-Integrate cell manufacturing platform and by multiplexing its HPV TCR with additional TCRs in its TSC-2xx series of cell therapy candidates. TScan has used the large cargo capacity of T-Integrate to include in the TSC-200 construct features that enable engineering of both cytotoxic and helper T cells and features designed to help confer resistance to the immunosuppressive micro-environment of solid tumors.

TScan has recently discovered a novel HLA-C*07:02-restricted epitope encoded by the well-known cancer/testis gene MAGE-A1, using its TargetScan platform. This cancer-specific gene is frequently overexpressed in a wide variety of solid tumors. In the U.S., the target is expressed in as many as 45% of head & neck cancer patients, 50% of melanoma patients, 50% of cervical cancer patients and 50% of non-small cell lung cancer patients. The TCR that recognizes this novel epitope was isolated from a patient with head & neck cancer who exhibited an exceptional response to immune checkpoint inhibitor therapy. TScan has launched a new program, TSC-204, that will include multiple TCRs for different HLA-restricted epitopes on this same protein. TScan believes that it is the only company with a disclosed TCR program in MAGE-A1 for HLA types other than A*02:01. The Company has now advanced TSC-204 into lead TCR-T therapy candidate optimization.

The Company expanded its management team with the appointments of Zoran Zdraveski, J.D., Ph.D., as Chief Legal Officer, and Heather Savelle as Vice President, Investor Relations.

In July 2021, TScan completed its initial public offering, raising $100 million in aggregate gross proceeds, before deducting underwriting discounts and commissions and offering expenses, and began trading on The Nasdaq Global Market. The IPO followed the closing of a Series C preferred stock financing of $100 million in gross proceeds in January 2021.

In July 2021, Gavin MacBeath, Ph.D., TScan’s Chief Scientific Officer, presented findings from TScan’s work to discover the targets of T cells in recovering COVID-19 patients at the Cell-Mediated Therapies for Infectious Disease Summit. The presentation also featured in vitro data comparing several polyepitope T cell vaccine candidates based on the Company’s novel T cell target discoveries. TScan is now advancing these T cell-eliciting vaccine candidates through pre-clinical development with the goal of engineering a COVID-19 vaccine that generates long-term immunity with less susceptibility to resistance from emerging variants. In addition to addressing the current pandemic, this program represents proof-of-concept for a novel class of vaccines that are designed to elicit a long-lasting T cell response to infectious pathogens.

Upcoming Expected Milestones and Key Priorities

Liquid Tumor Programs: TScan’s two lead liquid tumor TCR-T therapy candidates, TSC-100 and TSC-101, are designed to target HA-1 and HA-2, respectively, and treat patients with hematological malignancies who are undergoing allogeneic hematopoietic stem cell transplantation.

TScan will present two posters related to TSC-100 and TSC-101 at the upcoming ASH (Free ASH Whitepaper) Annual Meeting and Exposition.

IND-enabling studies and the submission of IND applications to the U.S. Food and Drug Administration (FDA) are planned for TSC-100 and TSC-101 during the fourth quarter 2021.

Following the IND submissions and pending acceptance by the FDA, clinical trials for TSC-100 and TSC-101 are expected to begin in the first half of 2022 with preliminary data expected in the second half of 2022.

Solid Tumor Programs: TScan’s TSC-200 series of TCR-T therapy candidates include a combination of known targets, such as HPV16 for TSC-200, PRAME for TSC-203, and MAGE-A1 for TSC-204, as well as targets that are novel antigens for TCR-T therapy, such as those for TSC-201 and TSC-202.

TScan plans to present preclinical data of the TSC-2xx series during the first half of 2022.

·TScan plans to progress IND-enabling studies for the TSC-2xx series and submit IND applications during the second half of 2022, including for TSC-200 for HPV, during the second half of 2022. Further INDs are planned for 2023.

Infectious Disease Program

Research is continuing into potential T cell-focused COVID-19 vaccine constructs utilizing TScan’s novel T cell target discoveries.

Third Quarter 2021 Financial Results

As of September 30, 2021, the Company had cash and cash equivalents totaling $182.3 million, excluding restricted cash of $0.6 million. Based on the Company’s current operating plan, TScan expects that cash and cash equivalents as of September 30, 2021, will enable it to fund its operating expenses into 2024.

Research and development expenses for the third quarter 2021 were $14.2 million, compared to $5.8 million for the third quarter 2020.

General and administrative expenses for the third quarter 2021 were $4.0 million, compared to $1.6 million for the third quarter 2020.

Net loss for the third quarter 2021 was $15.8 million or $0.80 per common share, compared to a net loss of $7.2 million or $7.16 per common share for the third quarter 2020. Net loss per share was calculated using 19.9 million weighted average common shares and 1.0 million weighted average common shares outstanding for the third quarter of 2021 and 2020, respectively.

On July 20, 2021, the Company issued 6,666,667 shares of common stock in its IPO, raising gross proceeds of $100 million. In addition, upon closing of the IPO, all of the Company’s outstanding shares of convertible preferred stock automatically converted into 15,616,272 shares of common stock (of which 5,143,134 shares are non-voting common stock). This brings the total shares outstanding as of November 5, 2021, to 23,768,036, which consists of 18,624,902 shares of voting common stock and 5,143,134 shares of non-voting common stock.

TScan’s latest presentation is available on the "Events and Presentations" section of the Company’s website, and can be accessed here.