On November 10, 2021 Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, reported third quarter 2021 financial results and provided business updates (Press release, Seres Therapeutics, NOV 10, 2021, View Source [SID1234595135]).

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"We have made considerable progress across our organization, highlighted by the achievement of target enrollment in our investigational SER-109 recurrent C. difficile infection (rCDI) open-label study, and continued preparations for a BLA filing with the U.S. Food and Drug Administration (FDA). Along with our commercialization collaborator Nestlé Health Science and its Aimmune business, our organization continues to prepare for a successful launch of SER-109. Recently, we entered into a collaboration with Bacthera A.G., a global leader in biopharmaceutical product manufacturing, that expands our existing capabilities for commercial product supply. We intend to offer, pending approval, the first approved microbiome therapy to individuals living with rCDI, a patient group in urgent need of safe and effective new treatment options," said Eric Shaff, Chief Executive Officer at Seres.

Program and Corporate Updates

SER-109 Phase 3 ECOSPOR III study in recurrent C. difficile infection: SER-109, an investigational oral, live microbiome therapeutic, achieved its primary endpoint of superiority to placebo in reducing CDI recurrence at week 8 in Seres’ Phase 3 clinical trial in patients with rCDI.

Seres has achieved target enrollment in its open-label study of SER-109 in patients with rCDI (ClinicalTrials.gov identifier: NCT03183128), which also admits patients with a single recurrence of rCDI, to expand the SER-109 safety database. Based on FDA commentary, Seres believes the ECOSPOR III efficacy results should support a BLA filing as a single pivotal study. Seres intends to seek agreement with the FDA to begin a rolling submission of the BLA for SER-109 in the first half of 2022 and finalize the submission with data from the safety database in mid-2022.

Seres continues to execute activities necessary to support a SER-109 BLA submission, while also preparing for a successful product launch with Nestlé Health Science. The Company believes that a substantial commercial opportunity exists for SER-109. The cost of a patient with recurrence of CDI has been estimated to result in approximately $34,000 in annual direct healthcare expenses. There are approximately 170,000 cases of rCDI annually in the U.S.

In November, the Company initiated a SER-109 expanded access program at various sites across the United States. The program is designed to enable eligible adults with recurrent CDI to obtain access to SER-109 prior to a potential FDA product approval.

In October, Seres announced the presentation of an exploratory analysis of its SER-109 Phase 3 ECOSPOR III study at the American College of Gastroenterology 2021 Annual Meeting. Data from that study demonstrated that SER-109 reduced the risk of rCDI, as compared to subjects administered placebo, in individuals with risk factors for recurrence, including those taking acid-reducing medications such as proton pump inhibitors (PPIs) and H2 blockers.

In a separate press release issued today, Seres and Bacthera announced a collaboration to manufacture SER-109 in support of successful product commercialization. Under the terms of the agreement, Bacthera is establishing a dedicated facility floor for commercial manufacturing in its new Microbiome Center of Excellence, a manufacturing site dedicated to the production of live biotherapeutic products located in Visp, Switzerland. The manufacturing agreement between Bacthera and Seres aims to expand upon commercial manufacturing efforts currently in place.

In September, Seres presented multiple posters and an oral session highlighting SER-109 and SER-155 data at the IDWeek 2021 Virtual Conference. Results from the SER-109 Phase 3 study revealed that SER-109 was associated with significant improvements in rCDI patient quality of life with improved overall and mental health scores compared to baseline regardless of clinical outcome, as measured by CDiff32. Seres also presented an analysis showing that despite more than half of the patient population in ECOSPOR III having at least one co-morbidity, SER-109 was observed to significantly reduce the incidence of recurrence compared to placebo in these patients. SER-109 was observed to reduce C. difficile infection recurrence among patients at risk for recurrence because of age, gender, PPI use, and/or co-morbidities such as diabetes, cardiac disease and malignancy, in comparison to placebo.

In July, Seres announced that it had entered into agreement with Nestlé Health Science, and working with its Aimmune division, to jointly commercialize SER-109 in the United States and Canada. Under the terms of the agreement, Seres received an upfront license payment of $175 million, and is eligible for an additional $125 million upon FDA approval of SER-109 and $10 million upon approval in Canada. The agreement includes sales target milestones which, if achieved, could total up to $225 million. Seres will be responsible for development and pre-commercialization costs in the U.S. Upon commercialization, Seres will be entitled to an amount equal to 50% of the commercial profits.

SER-155 Phase 1b clinical study activities: Seres continues to prepare to initiate its SER-155 Phase 1b clinical study in collaboration with Memorial Sloan Kettering Cancer Center and the University of Chicago. SER-155 is an investigational oral, rationally-designed, cultivated microbiome therapeutic designed to reduce the incidence of gastrointestinal infections, bacteremia, and graft versus host disease (GvHD) in immunocompromised patients, including patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT). SER-155 is a consortium of bacterial species selected using Seres’ reverse translation discovery and development platforms. The design incorporates microbiome biomarker data from human clinical data and nonclinical human cell-based assays and in vivo disease models. The SER-155 composition aims to decrease infection and translocation of antibiotic-resistant bacteria in the gastrointestinal tract and modulate host immune responses to decrease GvHD. In addition to SER-109, SER-155 represents Seres second active development program in its infectious disease therapeutic area franchise.

In September, Seres presented preclinical data at IDWeek 2021 showing that SER-155 can decolonize antibiotic-resistant pathogens, potentially reducing the risk of subsequent infection.

In June, Seres announced data from its collaboration with the University of Cologne demonstrating that decreased microbiome diversity in allo-HSCT recipients is associated with poor clinical outcomes including mortality and increased incidence of intestinal GvHD. The data were presented at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. A separate poster presentation, including data from a collaboration with Memorial Sloan Kettering Cancer Center, established a significant association between microbiome composition and response to immune checkpoint inhibitor treatment in patients who have metastatic melanoma, metastatic lung, urothelial, or renal cancer.

SER-287 Phase 2b ECO-RESET study in ulcerative colitis: In July, Seres announced topline results from the Phase 2b ECO-RESET study evaluating SER-287, a donor-derived investigational microbiome therapeutic candidate, in patients with mild-to-moderate ulcerative colitis (UC). The SER-287 Phase 2b ECO-RESET study was a randomized, placebo-controlled, three-arm induction trial that enrolled 203 patients with active mild-to-moderate UC who had inadequate response or loss of response on prior therapy. The study did not meet its primary endpoint of improving clinical remission rates compared to placebo. Both dosing regimens of SER-287 were generally well tolerated. Given the lack of a clinical efficacy signal identified in ECO-RESET, the Company decided to close the open-label and maintenance portions of the study. The Company expects to obtain SER-287 Phase 2b study microbiome data in the second half of 2021.

SER-301 Phase 1b study in adults with mild-to-moderate ulcerative colitis: Seres is enrolling its Phase 1b study for SER-301, an investigational oral, rationally-designed, cultivated microbiome therapeutic. SER-301 is being evaluated in adults with mild-to-moderate UC. The study is being conducted in Australia and New Zealand and is designed to enroll approximately 65 subjects. The study objectives are to evaluate drug safety and pharmacokinetics and to evaluate clinical remission and other measures of efficacy as secondary endpoints.

The consortia of bacteria in SER-301 is designed to modify the microbiome and microbe-associated metabolites in the gastrointestinal tract and modulate pathways linked to gastrointestinal inflammation and epithelial barrier integrity in patients with UC. SER-301 was designed and optimized using Seres’ reverse translation discovery and development platforms. The SER-301 composition incorporated insights on the engraftment dynamics of different bacteria and also the association of specific bacteria with the modulation of inflammatory and immune pathways in human subjects that have been observed across Seres’ broader clinical portfolio and confirmed using Seres’ nonclinical human-cell based assays and in vivo models.

Financial Results

Seres reported net income of $68.2 million for the third quarter of 2021, as compared with a net loss of $30.3 million for the same period in 2020. The third quarter net income was driven primarily by collaboration revenue recognized from the co-commercialization license agreement with Nestlé Health Science.

Research and development expenses for the third quarter of 2021 were $39.9 million, as compared with $23.9 million for the same period in 2020. The research and development expenses were primarily related to Seres’ late-stage SER-109 clinical development program and manufacturing costs, as well as personnel expenses.

General and administrative expenses for the third quarter of 2021 were $19.6 million, as compared with $7.6 million for the same period in 2020. General and administrative expenses were primarily due to personnel expenses, professional fees and facility costs.

As of September 30, 2021, Seres had approximately $353.2 million in cash, cash equivalents and marketable securities as compared with approximately $229.4 million at the end of the second quarter 2021.

Conference Call Information

Seres’ management will host a conference call today, November 10, 2021, at 8:30 a.m. ET. To access the conference call, please dial 844-277-9450 (domestic) or 336-525-7139 (international) and reference the conference ID number 1275436. To join the live webcast, please visit the "Investors and News" section of the Seres website at www.serestherapeutics.com.

A webcast replay will be available on the Seres website beginning approximately two hours after the event and will be archived for at least 21 days.

On November 10, 2021 Castle Biosciences, Inc. (Nasdaq: CSTL), a company applying innovative diagnostics to inform disease management decisions and improve patient outcomes, reported that Derek Maetzold, president and chief executive officer, and Frank Stokes, chief financial officer, are scheduled to present a company overview at the Canaccord Genuity Virtual MedTech, Diagnostics and Digital Health & Services Forum on Thursday, Nov. 18, 2021, at 9:30 a.m. Eastern time (Press release, Castle Biosciences, NOV 10, 2021, View Source [SID1234595134]).

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Live audio webcasts of the company’s presentations will be available by visiting Castle Biosciences’ website at View Source Replays of the webcasts will be available for two weeks following the conclusion of the live broadcasts.

On November 10, 2021 SCYNEXIS, Inc. (NASDAQ: SCYX), a biotechnology company pioneering innovative medicines to overcome and prevent difficult-to-treat and drug-resistant infections, reported financial results for the third quarter ended on September 30, 2021 and provided an update on recent clinical and corporate developments (Press release, Scynexis, NOV 10, 2021, View Source [SID1234595133]).

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"We are rapidly advancing every element of the BREXAFEMME commercial launch according to plan, and our efforts have been paying off," said Marco Taglietti, M.D., President and Chief Executive Officer of SCYNEXIS. "Physician and payer receptivity to the BREXAFEMME value proposition is extremely encouraging as we continue to see an impressive upward trajectory of prescriptions and expanded coverage during the initial stages of the launch. We also look forward to reporting top-line data from our Phase 3 CANDLE study by early Q2 of next year. Furthermore, we are thrilled to announce the successful completion of the Phase 1 study of our new IV formulation of ibrexafungerp which will enable us to further expand the potential range of indications in the hospital setting."

BREXAFEMME Commercial Update

BREXAFEMME delivered $0.5 million in net sales in its first partial quarter of launch. IQVIA data showed 1,006 total prescriptions for BREXAFEMME in Q3 2021, with nearly 700 in September, which was in line with the company’s internal expectations for the first partial quarter of launch. There was a consistent week-over-week growth rate of prescriptions from early August to the end of the quarter, and a similar trajectory of growing positive momentum continuing into the fourth quarter, with IQVIA showing 1,100 BREXAFEMME prescriptions in October alone.
Insurance coverage of BREXAFEMME continues to grow. BREXAFEMME is now covered by commercial insurance plans that represent more than 30% of commercially covered lives in the U.S.
Ibrexafungerp Clinical Updates

Enrollment is complete in the Phase 3 CANDLE study, investigating the efficacy and safety of oral ibrexafungerp for the prevention of recurrent vulvovaginal candidiasis (rVVC), for which there is no approved therapy in the U.S. As previously reported, SCYNEXIS is on target to have last-patient/last-visit by the end of 2021 with top-line results by early Q2 2022. A supplemental NDA submission is anticipated in Q2 2022 with a potential approval in late 2022.
Reported successful completion of Phase 1 clinical study of liposomal IV formulation of ibrexafungerp. SCYNEXIS reported the successful completion of its Phase 1 randomized, double-blind, placebo-controlled single and multiple ascending dose study evaluating the safety, tolerability, and pharmacokinetics of the liposomal IV formulation of ibrexafungerp in healthy subjects. Dosing began in March 2021, and the last cohort completed in October 2021. Results from progressive ascending dosing to reach target exposure showed IV ibrexafungerp was generally well tolerated with no concerning safety findings, and SCYNEXIS is evaluating next steps toward the registrational program for this formulation.
Ongoing enrollment in the Phase 2 SCYNERGIA study for patients with invasive aspergillosis will be extended into 2022 to provide investigators impacted by the COVID-19 pandemic additional time to secure patients for this important trial. SCYNERGIA, which is evaluating oral ibrexafungerp in combination with voriconazole for the treatment of invasive pulmonary aspergillosis, has not enrolled as rapidly as initially projected. The prioritization of hospital resources toward addressing the COVID-19 pandemic has impacted the ability of many institutions to focus on screening and enrolling patients into some clinical trials, including SCYNERGIA. With recent decreases in COVID-19 hospitalizations in some regions, enrollment is expected to accelerate over the next two quarters. Top-line results are anticipated in the second half of 2022.
Ibrexafungerp Scientific Presentations and Publications

Key findings from interim data analyses of SCYNEXIS’ ongoing refractory invasive fungal infections (rIFI) program, which is comprised of two open-label Phase 3 studies (FURI and CARES), were presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID). On July 12, 2021, presentations examining positive data from the third interim analysis of the FURI study and first interim analysis of the CARES study, showed oral ibrexafungerp’s strong clinical activity and ability to treat severe fungal infections in the hospital setting, including the treatment of patients with refractory fungal disease and invasive candidiasis and candidemia due to Candida auris, a high-mortality infection. The results support continued enrollment in both open-label Phase 3 studies, with potential future submissions under the LPAD regulatory pathway.

Two oral presentions on pooled data from SCYNEXIS Phase 3 VANISH program were presented at the Infectious Diseases Society for Obstetrics & Gynecology (IDSOG) 2021 Virtual Annual Meeting held on July 29-30, 2021. The presentations showed consistent efficacy of oral ibrexafungerp in the treatment for VVC, particularly in important patient sub-populations.
Three presentations from an interim analysis of a Phase 3 open-label study (FURI) were presented at Virtual IDWeek 2021 on September 29-October 3, 2021. These data support the favorable clinical activity of oral ibrexafungerp in severe hospital-based fungal infections across multiple serious fungal infections, including refractory candidiasis, oropharyngeal and esophageal candidiasis, and in Candida bone and joint infections.
Pre-clinical data supporting the potential of ibrexafungerp, to treat mucormycosis using an in vivo mouse model of mucormycosis, were presented at the 10th Trends in Medical Mycology (TIMM) meeting. On October 8-11, 2021, investigators presented findings, from an NIH-funded trial in which ibrexafungerp monotherapy demonstrated survival benefits equivalent to current standard of care treatments, including liposomal amphotericin B and posaconazole. Additionally, the study found when ibrexafungerp was combined with amphotericin B, synergistic benefits were observed with a significant enhancement in median survival time and overall survival when compared to any one therapy alone.
Corporate Developments

On September 13, 2021, SCYNEXIS announced that its partner, Hansoh Pharmaceutical Group Company Limited (Hansoh Pharma), had filed an investigational new drug (IND) application with the National Medical Products Administration (NMPA) of the People’s Republic of China for a Phase 3 study evaluating the efficacy and safety of ibrexafungerp for the treatment of VVC.

On October 26, 2021, Eric Francois, Chief Financial Officer of SCYNEXIS, notified the company of his intent to resign to return to his prior career in investment banking. SCYNEXIS has engaged Danforth Advisors, LLC, which is providing an interim Chief Financial Officer until a permanent replacement is found. Mr. Francois will continue in his current role through November 19, 2021, to complete the company’s third quarter reporting obligations and facilitate a smooth transition to Lawrence Hoffman, CPA, ESQ, of Danforth Advisors, who will serve as interim Chief Financial Officer.
Third Quarter 2021 Financial Results

BREXAFEMME generated a total of $0.5 million in net product revenues between the first week of August and September 30, 2021, which is in line with internal expectations.

Cost of product revenues was $0.1 million for the three months ended September 30, 2021 compared to $0.0 million for the three months ended September 30, 2020.

Research and development expense for the three months ended September 30, 2021 decreased to $4.4 million from $8.0 million for the three months ended September 30, 2020. The decrease of $3.6 million, or 45%, for the three months ended September 30, 2021, was primarily driven by a decrease of $1.6 million in chemistry, manufacturing, and controls (CMC) expense, a decrease of $1.2 million in clinical development expense, a decrease of $0.6 million in regulatory expense, and a net decrease in other research and development expense of $0.2 million.

Selling, general & administrative expense for the three months ended September 30, 2021 increased to $15.4 million from $3.5 million for the three months ended September 30, 2020. The increase of $11.9 million, or 341%, for the three months ended September 30, 2021, was primarily driven by a $8.7 million increase in commercial related expense associated with the ongoing commercialization of BREXAFEMME, an increase of $1.3 million in salary related costs, an increase of $0.7 million in expense associated with increased information technology costs, an increase of $0.7 million in medical affairs expense, and a net increase of $0.5 million in other selling, general and administrative expense.

Total other income was $18.8 million for the three months ended September 30, 2021, compared to total other income of $12.4 million for the three months ended September 30, 2020. During the three months ended September 30, 2021 and 2020, SCYNEXIS recognized non-cash gains of $18.8 million and $7.8 million, respectively, on the fair value adjustment of the warrant liabilities and during the three months ended September 30, 2021, and 2020, recognized non-cash gains of $1.4 million and $5.3 million on the fair value adjustment of the derivative liabilities, respectively.

Net loss for the three months ended September 30, 2021, was $0.6 million, or ($0.02) net loss per basic and ($0.06) net loss per diluted share, compared to net income of $0.9 million, or $0.09 net income per basic and ($0.28) net loss per diluted share for the three months ended September 30, 2020.

Cash and cash equivalents totaled $100.1 million on September 30, 2021, compared to $93.0 million in cash and cash equivalents on December 31, 2020. Based upon its existing operating plan, the company believes that its existing cash and cash equivalents, the sale of a portion of its New Jersey NOLs, and the anticipated sales of BREXAFEMME will enable SCYNEXIS to fund its operating requirements into 2023.

About Ibrexafungerp

Ibrexafungerp [pronounced eye-BREX-ah-FUN-jerp] is an antifungal agent and the first representative of a novel class of structurally-distinct glucan synthase inhibitors, triterpenoids. This agent combines the well-established activity of glucan synthase inhibitors with the potential flexibility of having oral and intravenous (IV) formulations. Ibrexafungerp is in late-stage development for multiple indications, including life-threatening fungal infections caused primarily by Candida (including C. auris) and Aspergillus species in hospitalized patients. It has demonstrated broad-spectrum antifungal activity, in vitro and in vivo, against multidrug-resistant pathogens, including azole- and echinocandin-resistant strains.The New Drug Application (NDA) for BREXAFEMME (ibrexafungerp tablets) was approved by the U.S. Food and Drug Administration (FDA) on June 1, 2021. FDA also granted Qualified Infectious Disease Product (QIDP) and Fast Track designations for the IV and oral formulations of ibrexafungerp for the indications of invasive candidiasis (IC) (including candidemia) and invasive aspergillosis (IA), and has granted Orphan Drug Designation for the IC and IA indications. Ibrexafungerp is formerly known as SCY-078.

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 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.