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.

On November 10, 2021 Sutro Biopharma, Inc. (NASDAQ: STRO), a clinical-stage drug discovery, development and manufacturing company focused on the application of precise protein engineering and rational design to create next-generation cancer and autoimmune therapeutics, reported its financial results for the quarter ended September 30, 2021, its recent business highlights, and a preview of anticipated select milestones in the remainder of 2021 (Press release, Sutro Biopharma, NOV 10, 2021, View Source [SID1234595130]).

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"We are pleased to announce that enrollment has been completed for the STRO–002 Phase 1 dose-expansion cohort for patients with advanced ovarian cancer. Additionally, we are prioritizing the STRO-002 franchise through additional studies, given the potential for this to be an important treatment option for patients with FolRα-expressing tumors," said Bill Newell, Sutro’s Chief Executive Officer. "For our STRO-001 program, we continue with dose escalation to achieve a recommended Phase 2 dose and support the work of our partner, BioNova, in Greater China, to explore the therapeutic potential in less heavily pretreated patients with multiple myeloma, non-Hodgkin’s lymphoma, and acute myeloid leukemia."

Recent Business Highlights and Anticipated 2021 Select Milestones

STRO-002, FolRα-Targeting Antibody-Drug Conjugate (ADC): STRO-002 is being studied in patients with ovarian cancer and endometrial cancer.

The patient enrollment of 40 patients has been completed for the Phase 1 dose-expansion cohort for advanced ovarian cancer, with participation from clinical sites across the U.S. and in Spain.
Sutro is expected to report initial data for the dose-expansion cohort in the second half of 2021; the data are expected to inform regulatory discussions and registration strategy, including the planned identification of patient populations that may benefit optimally from treatment with STRO–002.
Sutro has opened a new cohort of the Phase 1 dose-expansion study of STRO-002 for endometrial cancer and is currently enrolling patients. A STRO-002 study in combination with bevacizumab has cleared protocol and the first patient is expected later this year.
Nonclinical data on STRO-002 as a potential therapeutic targeting a rare pediatric acute myeloid leukemia (AML) subtype expressing FolRα will be presented by investigators at the Fred Hutchinson Cancer Research Center (Fred Hutch) as an oral presentation at the 63rd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH 2021). Details are as follows:
Publication Number:

209

Presentation Title:

Targeting FOLR1 in High-Risk CBF2AT3-GLIS2 AML with STRO-002 FOLR1-Directed Antibody-Drug Conjugate

Presentation Time:

Saturday, December 11, 2021, at 3:00 PM ET

Session Name:

604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Novel Molecular Therapies in AML

STRO-001, CD74-Targeting ADC: The Phase 1 study for patients with B–cell malignancies, including patients with non-Hodgkin’s lymphoma and multiple myeloma, continues with dose escalation.

Dose escalation is ongoing to achieve a recommended phase 2 dose (RP2D), with the last reported doses of 5.0 mg/kg in the multiple myeloma (MM) cohort and 4.2 mg/kg in the non-Hodgkin’s lymphoma (NHL) cohort.
Nonclinical data on STRO-001 as a potential therapeutic targeting AML and acute lymphoblastic leukemia (ALL) will be presented by investigators at the Fred Hutch as an oral presentation at ASH (Free ASH Whitepaper) 2021. Details are as follows:
Publication Number:

509

Presentation Title:

Therapeutic Targeting of CD74 with STRO-001 Antibody-Drug Conjugate in AML and ALL

Presentation Time:

Sunday, December 12, 2021, at 5:30 PM ET

Session Name:

604. Molecular Pharmacology and Drug Resistance: Myeloid Neoplasms: Novel Strategies to Overcome Resistance to BCL-2 Inhibition

Additional Pipeline: Research and preclinical development are underway for several internal candidates.

Sutro announced multiple discovery and preclinical candidates, including ADCs targeting ROR1 and Tissue Factor, a 5T4-CD3 bispecific T-Cell Engager (TCE), and cytokine derivatives, including IFNα and IL-12.
Discovery and preclinical work on these programs are underway to determine Sutro’s next program to advance to the clinic.
Collaboration Updates: Sutro continues to seek to maximize the value of its cell-free platform by working with partners on programs in multiple disease spaces and geographies.

In October of this year, Sutro entered into a collaboration with BioNova Pharmaceuticals Limited (BioNova) to assess the therapeutic potential for STRO-001 in potentially less heavily pretreated patient populations with MM, NHL, and AML within Greater China, including mainland China, Hong Kong, Macau, and Taiwan.
Merck extended the first cytokine derivative research program by up to two years to continue the work on an additional candidate. Sutro received an initial payment of $2.5 million and is eligible to receive up to a total of $10 million in connection with the research program extension.
Sutro continues to manufacture clinical trial material for Bristol Myers Squibb’s (BMS) CC-99712, a BCMA–targeting ADC, for treatment of patients with multiple myeloma.
Third Quarter 2021 Financial Highlights
Cash, Cash Equivalents and Marketable Securities
As of September 30, 2021, Sutro had cash, cash equivalents and marketable securities of $254.2 million, as compared to $326.5 million as of December 31, 2020, with projected runway into the second half of 2023, based on current business plans and assumptions. The above balance does not include the value associated with Sutro’s holdings of Vaxcyte common stock.

Unrealized Gain from Increase in Value of Vaxcyte Common Stock
As of September 30, 2021, Sutro held approximately 1.6 million shares of Vaxcyte common stock, with a fair value of $39.8 million. The non-operating, unrealized gain of $4.5 million for the three months ended September 30, 2021 was due to the increase since June 30, 2021 in the estimated fair value of Sutro’s holdings of Vaxcyte common stock. Vaxcyte common stock held by Sutro will be remeasured at fair value based on the closing price of Vaxcyte’s common stock on the last trading day of each reporting period, with any non-operating, unrealized gains and losses recorded in Sutro’s statements of operations.

Revenue
Revenue was $8.5 million for the three months ended September 30, 2021, as compared to $17.8 million for the same period in 2020, related principally to the Merck, BMS, and EMD Serono collaborations. Future collaboration revenue from Merck, BMS, EMD Serono, BioNova, and from any additional collaboration partners, will fluctuate as a result of the amount and timing of revenue recognition of upfront, milestones, and other collaboration agreement payments.

Operating Expenses
Total operating expenses for the three months ended September 30, 2021 were $43.2 million, as compared to $28.4 million for the same period in 2020. The 2021 period includes non-cash expenses for stock-based compensation of $6.5 million and depreciation and amortization of $1.1 million, as compared to $3.1 million and $1.0 million, respectively, in the comparable 2020 period. Total operating expenses for the three months ended September 30, 2021 were comprised of research and development expenses of $26.6 million and general and administrative expenses of $16.6 million, which are expected to increase in 2021 as Sutro’s internal product candidates advance in clinical development and additional general and administrative expenses are incurred as a public company.

On November 10, 2021 Affimed N.V. (Nasdaq: AFMD), a clinical-stage immuno-oncology company committed to giving patients back their innate ability to fight cancer, reported financial results for the quarter ended September 30, 2021, and provided an update on clinical and corporate progress (Press release, Affimed, NOV 10, 2021, View Source [SID1234595129]).

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"In the past months, we have significantly expanded our efforts to ensure the development of our leading candidates, AFM13 and AFM24, which we believe will result in multiple catalysts over the next several quarters," said Adi Hoess, CEO of Affimed. "We are excited about AFM28, a ROCK platform-based ICE, which we believe will be a novel and promising approach for difficult-to-treat AML patients. We know NK cells have shown some activity in AML and, coupled with what we are seeing in the AFM13 study in combination with NK cells we are hopeful that this highly differentiated product candidate will offer a new treatment option to those patients currently left behind," he concluded.

Clinical Stage Program Updates
AFM13 (CD30/CD16A)

Affimed is continuing to recruit patients in the REDIRECT study (AFM13-202) after reporting positive results from the preplanned interim futility analysis in March 2021; based on this successful interim analysis, the high- and low-CD30 expressing cohorts of this trial have been combined into one. Affimed expects to complete enrollment in the study in the first half of 2022.
REDIRECT is a phase 2, registration-directed study of AFM13 monotherapy in patients with relapsed or refractory CD30-positive peripheral T-cell lymphoma (PTCL).

Affimed reported that there were no dose-limiting toxicities observed in the dose escalation part of the investigator sponsored study (IST) at The University of Texas MD Anderson Cancer Center. The study, which is investigating the treatment of CD30-positive lymphoma patients with AFM13 precomplexed cord blood-derived natural killer (NK) cells (AFM13-104), continues to enroll patients at the highest dose level. As of October 31, 2021, 18 patients had been treated in the study, including 12 patients at the highest NK cell dose. An amendment to the protocol for the study has been submitted to allow for the enrollment of up to 40 patients at the highest dose level to generate additional data on safety and efficacy. The expansion would include patients with Hodgkin Lymphoma and non-Hodgkin Lymphoma. As presented at AACR (Free AACR Whitepaper) in April 2021, the first four patients showed a 100% objective response rate with two out of four patients (50%) achieving a complete response. Affimed expects to present additional data from the study at a company-sponsored event in December 2021.
AFM24 (EGFR/CD16A)

For AFM24, an EGFR/CD16A targeted innate cell engager (ICE) for patients with EGFR-expressing solid tumors, Affimed is executing a strategy intended to deliver the highest probability of success. As such, the objective is to treat patients with EGFR-expressing tumors with AFM24 as monotherapy (AFM24-101) in 3 indications, with AFM24 in combination with an anti-PD-L1 antibody (AFM24-102) in at least 3 indications and with AFM24 in combination with autologous NK cells in 3 indications (AFM24-103).
In AFM24-101, the monotherapy phase 1/2a clinical trial, a weekly dose of 480 mg has been identified as the recommended phase 2 dose based on a comprehensive review of safety, pharmacokinetic and pharmacodynamic data, including exposure and NK cell CD16A receptor occupancy. Of note, four out of six patients dosed in the 480 mg cohort remain on therapy based on investigator assessment of clinical benefit; two of these patients have demonstrated stable disease beyond three months and continue on treatment. Affimed expects to start the dose expansion phase of the trial at the recommended phase 2 dose in the fourth quarter of 2021. The trial will include the following indications:
Renal cell carcinoma (clear cell), failing standard of care (SoC) including TKIs and PD1 targeted therapy
Non-small cell lung cancer (EGFR-mutant), failing SoC TKIs and PD1 naïve; and,
Colorectal cancer, failing chemotherapy plus EGFR-targeted antibodies In parallel, Affimed will continue to evaluate higher doses of AFM24 to generate additional safety data, and enrollment has begun in a cohort to evaluate a weekly dose of 720 mg.
AFM24-102, the phase 1/2a combination study of AFM24 with the PD-L1 checkpoint inhibitor atezolizumab (Tecentriq) in EGFR-expressing solid tumors, is on track to start in the fourth quarter of 2021. The combination trial will include the following indications:
Non-small cell lung cancer (EGFR-wildtype), failing chemotherapy and PD1 targeted therapy
Gastric/gastroesophageal junction (GEJ) cancer failing chemotherapy and/or PD1 targeted therapy; and,
A basket of EGFR-expressing tumors comprising pancreatic, hepatocellular and biliary tract cancer failing standard of care therapy for the respective disease
AFM24-103, the phase 1/2a combination study of AFM24 with NKGen Biotech’s autologous NK cell therapy, SNK01, a first-in-human proof of concept trial in EGFR-expressing solid tumors, is now open to recruit patients. As previously announced, the combination trial will include the following indications:
Non-small cell lung cancer (EGFR-wildtype), failing chemotherapy and PD1 targeted therapy
Squamous cell carcinoma of the head and neck, failing chemotherapy and PD1 targeted therapy; and,
Colorectal cancer including those with mutations, failing standard of care therapy
Preclinical Program
AFM28 (CD123/CD16A)

Preclinical candidate AFM28, developed on the company’s proprietary ROCK platform, is a bispecific, tetravalent ICE that targets CD16A on NK cells and macrophages, as well as CD123 on leukemic cells and leukemic stem cells that are prevalent in AML. The high affinity to CD16 and CD123 initiates antibody-dependent cell-mediated cytotoxicity (ADCC) against CD123+ tumor cells.
Preclinical data demonstrates that AFM28 induces tumor cell lysis more potently than conventional anti-CD123 antibodies, even at low CD123 expression. Further, AFM28 shows a 100-fold more potent NK cell activation in an ex vivo analysis, compared to Fc-enhanced IgG1 antibodies. In a preclinical toxicology study in cynomolgus monkey, AFM28 was safe and well-tolerated and exhibited the expected pharmacodynamic activity suggesting a good safety profile and the potential to eliminate CD123+ cells in vivo. Clinical investigation of AFM28 is planned to start in second half of 2022.
Third Quarter 2021 Financial Highlights
(Figures for the quarters ended September 30, 2021, and 2020 are unaudited.)

As of September 30, 2021, cash and cash equivalents totaled €198.7 million compared to €146.9 million on December 31, 2020. Based on its current operating plan and assumptions, Affimed anticipates that its cash and cash equivalents will support operations into the second half of 2023.

Net cash used in operating activities for the quarter ended September 30, 2021 was €25.6 million compared to €3.6 million for the quarter ended September 30, 2020.

Total revenue for the quarter ended September 30, 2021, was €8.7 million compared with €10.5 million for the quarter ended September 30, 2020. Revenue predominately relates to the Genentech and Roivant collaborations.

Research and development expenses for the quarter ended September 30, 2021 amounted to €20.6 million compared to €10.1 million for the quarter ended September 30, 2020. The increase is largely due to increased costs for AFM24, including costs associated with the ongoing phase 1/2a clinical trial and manufacturing costs for clinical trial material required for the ongoing study and planned future studies, as well as an increase in costs associated with early-stage development/discovery activities. In addition, there was an increase associated with research and development that is non-project specific, including share-based payment expense, intellectual property-related expenses and facility costs.

General and administrative expenses were €6.8 million in the quarter ended September 30, 2021, compared to €3.5 million in the quarter ended September 30, 2020. The increase relates largely to higher personnel expenses due to an increase in headcount, higher premiums for our Directors and Officers liability insurance, increase in share-based payment expense and higher legal and consulting expenses.

Net finance income for the quarter ended September 30, 2021 was €1.5 million compared to net finance loss of €3.1 million in the quarter ended September 30, 2020. Net finance income/loss is largely due to foreign exchange gains/losses related to assets denominated in U.S. dollars as a result of currency fluctuations between the U.S. dollar and Euro during the quarter.

Net loss for the quarter ended September 30, 2021 was €17.1 million, or loss of €0.14 per common share, compared with a net loss of €6.0 million, or €0.07 loss per common share, for the quarter ended September 30, 2020.

The weighted number of common shares outstanding for the quarter ended September 30, 2021 was 119.8 million. Additional information regarding these results will be included in the notes to the consolidated financial statements as of September 30, 2021, of Affimed’s filings with the U.S. Securities and Exchange Commission (SEC).

Note on International Financial Reporting Standards (IFRS)
Affimed prepares and reports consolidated financial statements and financial information in accordance with IFRS as issued by the International Accounting Standards Board. None of the financial statements were prepared in accordance with Generally Accepted Accounting Principles in the United States. Affimed maintains its books and records in Euro. Conference Call and Webcast Information Affimed will host a conference call and webcast today, November 10, 2021, at 8:30 a.m. EST to discuss third quarter 2021 financial results and recent corporate developments. The conference call will be available via phone and webcast. To access the call, please dial +1 (409) 220-9054 for U.S. callers, or +44 (0) 8000 323836 for international callers, and reference passcode 6166004 approximately 15 minutes prior to the call.
A live audio webcast of the conference call will be available in the "Webcasts" section on the "Investors" page of the Affimed website at View Source A replay of the webcast will be accessible at the same link for 30 days following the call.