On November 15, 2021 VBL Therapeutics (Nasdaq: VBLT), a clinical stage biotechnology company developing first-in-class therapeutics for difficult-to-treat malignant solid tumors and immune or inflammatory indications, reported financial results for the third quarter ended September 30, 2021, and provided a corporate update (Press release, VBL Therapeutics, NOV 15, 2021, View Source [SID1234595620]).

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"We continue to execute on our development and strategic objectives which we believe positions 2022 as a potentially transformational year for VBL," said Dror Harats, M.D., Chief Executive Officer of VBL. "We look forward to completing the enrollment in the Phase 3 OVAL study in the first quarter of 2022 and the PFS co-primary endpoint top-line data readout in the second half of 2022. We also expect to initiate a first-in-human trial with VB-601, our monocyte targeting program, in the second half of 2022. With the recent strengthening of our management and board of directors, together with our newly established presence in the United States, we are taking important steps to prepare VBL for continued growth and the planned commercialization of VB-111."

Third Quarter of 2021 and Recent Corporate Highlights

Development Programs

More than 85% of the planned 400 patients have been enrolled in the OVAL study, a global registration-enabling Phase 3 clinical trial evaluating VB-111 in platinum-resistant ovarian cancer.
The independent Data Safety Monitoring Committee (DSMC) conducted its fifth pre-planned data review of the OVAL study and provided clearance to proceed as planned with no changes to the protocol.
The Chemistry, Manufacturing, and Controls group of the U.S. Food and Drug Administration provided VBL clearance of VB-111 batches produced in its commercial-scale facility located in Modiin, Israel, for use in the Company’s clinical trials in the United States.
Enrollment continues in the VB-111 investigator-sponsored Phase 2 clinical trials in recurrent glioblastoma multiforme (rGBM) and metastatic colorectal cancer (mCRC) with preliminary data expected from the mCRC study in the first half of 2022 and the rGBM study in the second half of 2022.
IND-enabling toxicology studies are underway for VB-601, a monoclonal antibody targeting monocytes for prevalent and chronic inflammatory disorders, and VBL expects to initiate a first-in-human clinical trial for the program in the second half of 2022.
Corporate

Further strengthened the management team with the appointment of Sam Backenroth as chief financial officer. In connection with the appointment, VBL established U.S. operations in New York, as the company prepares for anticipated growth.
Enhanced the board of directors (Board) with the appointments of Alison Finger and Michael Rice, who bring significant commercialization and capital markets expertise to VBL. Also completed the planned chairman succession to Marc Kozin, who initially joined the Board as vice chairman in October 2020.
Financial Results for the Third Quarter of 2021

At September 30, 2021, VBL had cash, cash equivalents, short-term bank deposits and restricted bank deposits of $50.8 million. After September 30, 2021, the company received a further $9.6 million in proceeds from warrant exercises. VBL expects that its cash, cash equivalents, short-term bank deposits, and restricted bank deposits will be sufficient to fund currently planned operating expenses and capital expenditures into the fourth quarter of 2023.
For the quarter ended September 30, 2021, VBL reported a net loss of $6.5 million, or ($0.09) per basic share, compared to a net loss of $5.8 million, or ($0.12) per basic share, in the comparable period in 2020.
Revenues for the quarter ended September 30, 2021, were $0.2 million, as compared to $0.2 million in the comparable period in 2020.
For the quarter ended September 30, 2021, total operating expenses were approximately $6.6 million, consisting of $5.0 million in research and development expenses, net, and $1.6 million in general and administrative expenses. This compares with total operating expenses of $5.9 million in the third quarter ended September 30, 2020, which was comprised of $4.6 million in research and development expenses, net, and $1.3 million in general and administrative expenses.

Webcast: View Source
The live webcast will be available online and may be accessed from the "Events and Presentation" page of VBL’s website. A replay of the webcast will be available beginning approximately one hour after the conclusion of the call and will remain available for at least 30 days thereafter.

On November 15, 2021 Roivant Sciences Ltd. (Nasdaq: ROIV), a next-generation biopharmaceutical company dedicated to improving the delivery of healthcare to patients, reported its financial results for the second fiscal quarter ended September 30, 2021 and provided an update on the Company’s operations (Press release, Roivant Sciences, NOV 15, 2021, View Source [SID1234595619]).

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Roivant’s Chief Executive Officer, Matt Gline, noted: "We are looking forward to this new phase of growth as we prepare to launch potential blockbuster tapinarof in psoriasis, with registrational studies in atopic dermatitis also underway. In addition to the studies underway at Dermavant, we expect at least four other programs will enter Phase 2 or Phase 3 trials in 2022, and we are excited to continue advancing our protein degrader programs towards the clinic, as well."

Recent Developments

Roivant: Roivant closed its business combination with Montes Archimedes Acquisition Corp. ("MAAC") and concurrent PIPE financing, and Roivant began trading on Nasdaq under the ticker "ROIV." Roivant also announced the appointment of its new Chief Financial Officer, Richard Pulik, who previously served as the Global Head of Business Development & Licensing and Portfolio Management, Oncology at Novartis.
Dermavant: At the 30th EADV Virtual Congress, Dermavant presented final results from the Phase 3 PSOARING 3 long-term extension study of tapinarof in patients with plaque psoriasis. The study results demonstrated that tapinarof was generally well tolerated long term, with a safety profile consistent with the pivotal studies and previously reported interim analysis of data from PSOARING 3. The study demonstrated a high rate of complete disease clearance, with 58.2% of patients who entered the study with a PGA score ≥2 achieving a PGA score of 0 or 1. The study also demonstrated improved and durable results for up to 52 weeks and a median remittive effect off-therapy of approximately four months for patients entering with a PGA score of 0.
Aruvant: At Roivant’s Annual R&D Day, Aruvant released clinical data from the third and fourth patients dosed in its ongoing Phase 1/2 trial of ARU-1801 in sickle cell disease. These patients, the first to be dosed with Aruvant’s updated manufacturing process, have had zero vaso-occlusive events 18 and 12 months after dosing, respectively. Punam Malik, M.D., Director of the Cincinnati Comprehensive Sickle Cell Center and Program Leader of the Hematology and Gene Therapy Program at the Cincinnati Children’s Hospital Medical Center, will present ARU-1801 data at 6:00 to 8:00 PM ET on December 13, 2021 at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.
Sio Gene Therapies: Sio Gene Therapies announced positive interim safety and biomarker data from its ongoing Phase 1/2 clinical trial of AXO-AAV-GM1 in GM1 gangliosidosis, showing consistent dose-dependent improvements across biomarker measures and no overt disease progression in six out of seven patients treated across low- and high-dose cohorts.
Major Upcoming Milestones

Dermavant: We expect a decision from the FDA on the approval of tapinarof for the treatment of adults with plaque psoriasis in the second quarter of calendar year 2022. We also expect to report topline data from Dermavant’s Phase 3 clinical trial of tapinarof for the treatment of atopic dermatitis in the first half of calendar year 2023.
Immunovant: Contingent upon FDA feedback, Immunovant plans to initiate a pivotal trial evaluating batoclimab for the treatment of myasthenia gravis in the early part of calendar year 2022, and re-initiate its programs in thyroid eye disease and warm autoimmune hemolytic anemia. Immunovant also plans to announce at least two new indications and submit INDs with their trial designs to the FDA by August 2022.
Aruvant: We expect Aruvant to report additional clinical data from its ongoing Phase 1/2 trial of ARU-1801 in sickle cell disease patients at ASH (Free ASH Whitepaper), including data that demonstrates how the potent anti-sickling effect of ARU-1801 can translate into robust clinical outcomes.
Kinevant: Kinevant remains on track to initiate its Phase 2 trial evaluating namilumab for the treatment of pulmonary sarcoidosis in the first half of calendar year 2022.
Lysovant: Lysovant remains on track to initiate its multiple ascending dose study of LSVT-1701 in patients with complicated Staph aureus bacteremia including infective endocarditis in the first half of calendar year 2022.
Fiscal Quarter Ended September 30, 2021 Financial Summary

Cash Position

As of September 30, 2021, we had cash and cash equivalents of approximately $2.5 billion. The increase from cash and cash equivalents of approximately $2.0 billion as of June 30, 2021 reflects net cash proceeds of $213.4 million received at the closing of the business combination with MAAC and concurrent PIPE financing, approximately $320 million in cash proceeds from Datavant’s merger with Ciox Health (the "Datavant Merger") and funding of the second $100.0 million payment to Proteovant Sciences under a subscription agreement entered into with SK, Inc. in December 2020.

Research and Development Expenses

Research and development (R&D) expenses were $254.3 million for the three months ended September 30, 2021 compared to $97.4 million for the three months ended September 30, 2020. The increase was primarily due to an increase in program-specific costs relating to our product candidates, one-time consideration for the purchase of in-process R&D related to an asset acquisition, and an increase in share-based compensation expense due to the achievement of the liquidity event vesting condition for restricted stock units, performance options and capped value appreciation rights upon the closing of the business combination with MAAC, resulting in the recognition of a one-time catch-up expense of $22.9 million. Non-GAAP R&D expenses were $103.9 million for the three months ended September 30, 2021 compared to $50.2 million for the three months ended September 30, 2020.

General and Administrative Expenses

General and administrative (G&A) expenses were $437.8 million for the three months ended September 30, 2021 compared to $59.7 million for the three months ended September 30, 2020. The increase was largely due to an increase in share-based compensation expense, primarily as a result of the achievement of the liquidity event vesting condition for restricted stock units, performance options and capped value appreciation rights upon the closing of the business combination with MAAC, resulting in the recognition of a one-time catch-up expense of $350.0 million. Non-GAAP G&A expenses were $68.6 million for the three months ended September 30, 2021 compared to $47.7 million for the three months ended September 30, 2020.

Gain on Sale of Investment

Gain on sale of investment resulted from the Datavant Merger in July 2021. At closing of the Datavant Merger, we received approximately $320 million in cash and a minority equity interest in the combined company, which resulted in a gain of $443.8 million.

Net Loss

Net loss for the three months ended September 30, 2021 was $225.6 million compared to $53.5 million for three months ended September 30, 2020. On a per common share basis, net loss was $0.32 and $0.06 for the three months ended September 30, 2021 and 2020, respectively. Non-GAAP net loss was $169.2 million for the three months ended September 30, 2021 compared to $96.9 million for the three months ended September 30, 2020.

(1) Represents non-cash share-based compensation expense.
(2) Represents one-time development milestone payments.
(3) Represents one-time in-process research and development expense.
(4) Represents a one-time gain on sale of investment resulting from the merger of Datavant and CIOX Health in July 2021.
(5) Represents the unrealized loss (gain) on equity investments in unconsolidated entities that are accounted for at fair value with changes in value reported in earnings. This is a non-cash loss (gain) that has no direct correlation to the operation of Roivant’s business.
(6) Represents the change in fair value of debt and liability instruments, which is non-cash and primarily includes the unrealized loss (gain) relating to the measurement and recognition of fair value on a recurring basis of certain liabilities.
(7) Represents the one-time gain on termination of the options held by Sumitomo Dainippon Pharma Co., Ltd. to purchase Roivant’s ownership interest in certain Vants (the "Sumitomo Options").
(8) Represents one-time gain on deconsolidation of a subsidiary and the remeasurement of a previously held interest in an unconsolidated entity upon its consolidation.
(9) Represents the estimated tax effect of the adjustments.

The information presented in this document has been prepared in accordance with U.S. generally accepted accounting principles ("GAAP"), unless otherwise noted as non-GAAP. Roivant believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. Management uses certain non-GAAP information internally for its operating, budgeting and financial planning purposes. Non-GAAP information is not prepared under a comprehensive set of accounting rules and should only be used to supplement an understanding of Roivant’s operating results as reported under GAAP. Non-GAAP financial information generally excludes (i) non-cash items, including share-based compensation expense and the change in fair value of debt and liability instruments, (ii) consideration for the purchase of in-process research and development through asset acquisitions and license agreements, including upfront cash payments, the fair value of equity liability instruments issued, and the fair value of certain future contingent consideration payments, and (iii) other items that are considered unusual or not representative of underlying trends of Roivant’s business. Non-GAAP measures may be defined and calculated differently by other companies in the same industry. Reconciliations of the non-GAAP financial measures to the most directly comparable GAAP financial measures are provided in the tables above.

Investor Conference Call Information

Roivant will host a live conference call and webcast at 8:00 a.m. ET on Monday, November 15, 2021 to report its second quarter 2021 financial results, and provide a corporate update.

To access the live conference call, please dial +1-844-224-1923 (domestic) or +1-214-989-7105 (international) and use conference ID 3545615. A webcast of the call will also be available under "Events & Presentations" in the Investors section of the Roivant website at https://investor.roivant.com/news-events/events. The archived webcast will be available on Roivant’s website after the conference call.

Upcoming Investor Events

Jefferies London Healthcare Conference on Wednesday, November 17, 2021 at 12:20 p.m. GMT
Evercore ISI HealthCONx Conference on Tuesday, November 30, 2021 at 2:15 p.m. ET

On November 15, 2021 Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage company ("Centessa" or "Company") leveraging its innovative asset-centric business model to discover, develop and ultimately deliver impactful medicines to patients, reported financial results for the quarter ended September 30, 2021, and provided a review of recent accomplishments and anticipated upcoming milestones (Press release, Centessa Pharmaceuticals, NOV 15, 2021, View Source [SID1234595618]).

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"This has been a very productive quarter, as we continued to build our team and shared the first two data updates since the formation of Centessa earlier this year. We announced positive topline data from our proof-of-concept study evaluating SerpinPC in severe hemophilia subjects and seek to move this program into registrational studies in 2022. More recently, in our Phase 1 Part B study evaluating ZF874 for the treatment of AATD, we reported encouraging proof-of-mechanism data from three initial PiMZ subjects and plan to provide an update in 2022 once we have data on PiZZ subjects at multiple doses. In addition to these exciting early results, we are continuing to progress programs across our entire portfolio," said Saurabh Saha, MD, PhD, Chief Executive Officer of Centessa.

Dr. Saha continued, "Our recent $300 million financing facility with Oberland Capital will provide additional financial flexibility to help further advance our portfolio and better enable the Company to pursue strategic business development opportunities."

Recent Business Highlights

Announced Positive Topline Data from Proof-of-Concept Study of SerpinPC in Severe Hemophilia A and B Subjects Not on Prophylaxis: In September, the Company, together with subsidiary ApcinteX Limited ("ApcinteX"), announced positive topline results from the Phase 2a part of AP-0101, the six-month repeat dose portion of the ongoing first-in-human proof-of-concept study evaluating SerpinPC in severe hemophilia A and B subjects. In the highest dose cohort, SerpinPC reduced the self-reported all bleeds Annualized Bleeding Rate ("ABR") by 88% during the last 12 weeks of treatment (pre-specified primary assessment period) as compared to the all bleeds ABR prospectively measured during the pre-exposure observation period. In this cohort, five out of eight subjects had zero or one bleed during the 12-week pre-specified primary assessment period and self-reported spontaneous joint bleeds ABR was reduced by 94%. SerpinPC was well-tolerated with no sustained elevations in D-dimer.

Demonstrated Proof-of-Mechanism in First Three PiMZ Subjects Dosed in Part B of Phase 1 Study Evaluating ZF874: In November, the Company, together with subsidiary Z Factor Limited ("Z Factor"), announced proof-of-mechanism data from the first three PiMZ subjects dosed in the ongoing repeat dose Phase 1 Part B study of ZF874 in subjects carrying at least one Z-mutated alpha-1-antitrypsin allele (PiXZ). These are the first clinical data that suggest a pharmacological chaperone may be able to sufficiently increase functional Z-A1AT to levels greater than 11 micromolar in individuals with the PiZZ genotype, levels that have been the basis for approval of the existing A1AT augmentation therapies. Because one subject showed a delayed, reversible increase in ALT and AST, the Company will be exploring lower doses and different dosing regimens. The Company is taking steps to increase enrollment by adding sites in the United Kingdom and intends to expand the study to the European Union.

Secured $300 Million Financing Facility with Oberland Capital Management LLC: In October, the Company entered into a $300 million financing facility ("Oberland Agreement"). Under the terms of the agreement, Oberland Capital Management LLC ("Oberland Capital") will purchase up to $300 million of 6-year, interest-only, senior secured notes from the Company, including $75 million funded in October, a total of $125 million available within 24 months at the option of the Company, and $100 million available to fund M&A, in-licensing, or other strategic transactions, at the option of the Company and Oberland Capital. The Company’s pro forma cash position as of September 30, 2021, following receipt of the net proceeds from the first tranche of notes in October, was $653.4 million.

Centessa Subsidiary, Orexia Therapeutics, Initiated Collaboration with Schrödinger to Discover Novel Orexin Receptor Agonists: In October, Orexia entered into an exclusive collaboration with Schrödinger focused on the discovery of novel therapeutics targeting the orexin-2 receptor ("OX2R"), which is known to play a role in a broad spectrum of sleep disorders including narcolepsy. The collaboration provides Orexia with substantial access to Schrödinger’s entire computational platform as well as Schrödinger’s extensive expertise in ultra-large-scale deployment of its technology.

Leadership Team Strengthened by Appointment of Chief Innovation Officer: In October, the Company announced the appointment of David Grainger, PhD, as Chief Innovation Officer. Dr. Grainger will be a member of the Company’s executive leadership team and will be responsible for the overall management of the scientific and research activities.
Upcoming Milestones

ApcinteX’s SerpinPC, an activated protein C inhibitor for Hemophilia: During 2022, the Company expects to launch a global full development plan aimed at one or more registrations to maximize the broad potential for SerpinPC in the hemophilia space. The Company also expects to provide an update in 2022 on the ongoing Phase 2a open-label extension study.

Palladio Biosciences’ lixivaptan, a vasopressin V2 receptor antagonist for Autosomal Dominant Polycystic Kidney Disease ("ADPKD"): By the end of 2021, the Company expects to report initial safety data from the ongoing open-label ALERT Study of subjects who previously discontinued JYNARQUE (tolvaptan) due to liver toxicity. The Company expects to dose the first subject in the registrational Phase 3 ACTION Study by 1Q 2022.

Z Factor’s ZF874, a Z-A1AT folding corrector for AATD: During 2022, the Company expects to report on additional PiMZ as well as PiZZ subjects from the expanded Phase 1 Part B. The Company anticipates starting a global Phase 2 study in 2Q 2022, with 6-month dosing to commence in 2H 2022 once a dose and regimen are established and chronic animal toxicology is completed.

Pega-One’s imgatuzumab, a non-fucosylated anti-epidermal growth factor receptor ("EGFR") monoclonal antibody ("mAb") for Advanced Cutaneous Squamous Cell Carcinoma ("CSCC"): The Company expects to initiate an open-label, single arm, Phase 2 trial of imgatuzumab in advanced CSCC by the end of 2021 and dose the first subject in 1Q 2022.

Capella Bioscience’s CBS001, an anti-LIGHT mAb for Idiopathic Pulmonary Fibrosis ("IPF"): In 1H 2022, the Company expects to submit a Clinical Trial Authorisation ("CTA") application with the UK Medicines and Healthcare products Regulatory Agency ("MHRA") for CBS001 and commence a Phase 1 study shortly thereafter.

Capella Bioscience’s CBS004, an anti-BDCA2 mAb for Systemic & Cutaneous Lupus Erythematosus ("SLE/CLE") and Systemic Sclerosis ("SSc"): In 2H 2022, the Company expects to submit an Investigational New Drug ("IND") application with the U.S. Food and Drug Administration ("FDA") for CBS004 and commence a Phase 1 study shortly thereafter.

Orexia Therapeutics’ oral orexin receptor agonist for Narcolepsy Type 1 ("NT1"), and other neurological disorders characterized by excessive daytime sleepiness: The Company is on track to select a candidate for its oral program and commence IND enabling activities in 2022.

Janpix Limited’s dual degrader of Signal Transducer and Activator of Transcription proteins 3 and 5 ("STAT3" and "STAT5") for Acute Myeloid Leukemia: By the end of 2021, the Company expects to select a candidate for the STAT3/5 program.

PearlRiver Bio’s small molecule kinase inhibitors for EGFR mutations in Non-Small Cell Lung Cancer ("NSCLC"): The Company is progressing an EGFR-C797S mutation inhibitor for the treatment of NSCLC and expects to report on ongoing candidate selection in 2022. The Company will not select a candidate for its exon20 mutation program in 2021 and is presently reviewing this program.
Third Quarter 2021 Financial Results

Cash Position: Cash and cash equivalents were $578.8 million as of September 30, 2021, compared to $613.8 million as of June 30, 2021, a reduction of $35 million. On a pro forma basis as of September 30, 2021, cash and cash equivalents were $653.4 million, inclusive of the net proceeds of $74.6 million from the first tranche received under the Oberland Agreement on October 4, 2021. Based on the current, non-risk-adjusted operating plan, the Company expects the cash and cash equivalents as of September 30, 2021, plus the net proceeds of the first tranche, supplemented by the additional funds available under the Oberland Agreement, if drawn, to fund its operations into mid-2024.

Research & Development ("R&D") Expenses: R&D expenses for the Company for the three months ended September 30, 2021, were $25.9 million, compared to $1.9 million for the Centessa Predecessor Group (comprised of Z Factor Limited, LockBody Therapeutics Ltd, and Morphogen-IX Limited, three of the Centessa Subsidiaries acquired in January 2021) for the three months ended September 30, 2020. The $23.9 million increase is primarily attributable to the growth in the portfolio of product candidates under development following the acquisition of the Centessa Subsidiaries in January 2021, as well as increased spending in the Centessa Predecessor Group.

General & Administrative ("G&A") Expenses: G&A expenses for the Company for the three months ended September 30, 2021, were $12.5 million, compared to $0.2 million for the Centessa Predecessor Group during the three months ended September 30, 2020. The $12.2 million increase is primarily attributable to public company costs, the operating costs of Centessa Pharmaceuticals plc and Centessa Pharmaceutical Inc., including professional fees and personnel costs, and the increase in operating costs resulting from the acquired Centessa subsidiaries. In addition, the increase in personnel related expenses includes an increase in headcount and an increase in share-based compensation expense of $2.6 million which is primarily attributable to the equity awards issued at the time of the acquisition and the subsequent issuances of awards through September 30, 2021.

Net Loss: Net Loss attributable to common stockholders for the quarter ended September 30, 2021, was $40.2 million, or $0.45 per share, compared to a net loss of $2.1 million for the Centessa Predecessor Group for the quarter ended September 30, 2020.

On November 15, 2021 Instil Bio, Inc. ("Instil") (NASDAQ: TIL), a clinical-stage biopharmaceutical company focused on developing tumor infiltrating lymphocyte, or (TIL), therapies for the treatment of patients with cancer, reported its third quarter 2021 financial results and provided a corporate update (Press release, Instil Bio, NOV 15, 2021, View Source [SID1234595617]).

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"We have achieved key milestones in our continued development of ITIL-168 with clearance of our IND for the DELTA-1 study, Fast Track Designation approval and initiation of enrollment in DELTA-1," said Bronson Crouch, Chief Executive Officer of Instil. "Our progress in establishing a platform for cell therapy continues with the expansion of our UK clinical manufacturing capabilities which are on track to reach an annual capacity of over 200 lots by year end 2021 as well as with US clinical manufacturing coming online next year. With this added capacity, we expect to initiate additional trials in the months ahead as we progress both ITIL-168 and ITIL-306, our first genetically-engineered CoStAR-TIL."

Third Quarter 2021 Highlights and Recent Corporate Updates:

Clinical Development:

Received IND Clearance from the FDA to Initiate DELTA-1, a Phase 2 Clinical Trial for Patients with Advanced Melanoma: On September 13, 2021, Instil reported clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) to initiate DELTA-1, a global Phase 2 clinical trial of ITIL-168 with registrational intent in patients with advanced melanoma. The DELTA-1 trial was expanded during the IND review process in consultation with FDA to include additional populations of patients with advanced melanoma, including patients who discontinued PD-1 inhibitor therapy due to intolerable toxicity and patients who had an unsatisfactory response to prior PD-1 inhibitor.

Initiated enrollment in DELTA-1: Instil reported that patients have been enrolled and recruitment is ongoing into the pivotal study. Enrollment for Cohort 1 is expected to be completed within 12 months, with Cohorts 2 and 3 finishing enrollment thereafter. Instil expects top-line data and BLA filing submission in 2023 and a European Medicines Agency (EMA) marketing authorization application (MAA) filing in 2024.

ITIL-168 in Advanced Melanoma Granted FDA Fast Track Designation: Instil was recently granted Fast Track Designation from the U.S. FDA for ITIL-168 in advanced melanoma. Fast Track designation confers certain benefits on the development process, including more frequent communications with the FDA and potential eligibility for accelerated approval and priority review.

Readiness to Initiate DELTA-2 in H1 2022: Preparations are on track to initiate enrollment in DELTA-2, a Phase 1 study of ITIL-168 in non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), cervical cancer, and cutaneous squamous cell carcinoma (CSCC). Enrollment in DELTA-2 is planned to initiate in H1 2022.

Presented Clinical Data in Advanced Cutaneous Melanoma at ESMO (Free ESMO Whitepaper): Instil presented a subset analysis of treatment outcomes with TILs in 12 patients with checkpoint inhibitor-refractory advanced cutaneous melanoma, demonstrating a 58% objective response rates and median overall survival of 21.3 months; all patients in the subset analysis had experienced disease progression following treatment with a PD-1 inhibitor and CTLA-4 inhibition with ipilimumab.
Manufacturing and Technical Operations:

Clinical Manufacturing Readiness: U.K. manufacturing capacity remains on track for regulatory approval of the additional IMPACT manufacturing suite in Q4 2021, which will approximately triple the current U.K. manufacturing capacity. U.S. clinical manufacturing in Tarzana, CA remains on track for launch of clinical manufacturing in H1 2022, with qualification ongoing.
Research:

Appointed Mark Dudley, Ph.D. as Head of Research: Instil has appointed Mark Dudley, Ph.D. as Head of Research. Prior to Instil, Dr. Dudley led early development of T cell therapies at Adaptimmune Therapeutics plc, and before that was on the technical R&D leadership team at Novartis. Before Novartis, Dr. Dudley spent nearly two decades at the Surgery Branch of the National Cancer Institute, where he contributed to a diverse portfolio of experimental T cell therapies, including TIL, TCR-T, and CAR-T products. Dr. Dudley is a recognized pioneer in adoptive cell therapy, having published seminal studies in TIL therapy for refractory melanoma patients, and the first studies of CD19 CAR-T in humans, IL-2 and IL-12 genetically engineered T cells in clinical trials, and TCR-T cells in clinical trials.

Successful Pre-IND Meeting with FDA on First-in-Human Study of ITIL-306: Instil Bio recently completed a pre-IND meeting with the FDA for the proposed first-in-human Phase 1 study of ITIL-306, a TIL product genetically engineered to express a Costimulatory Antigen Receptor (CoStAR) molecule, to gain alignment on nonclinical, manufacturing, and clinical aspects of the program. The company expects initiate a Phase 1 study of ITIL-306 in multiple cancer indications in H1 2022.

Presented Pre-clinical Data on the CoStAR Platform at SITC (Free SITC Whitepaper): Instil presented posters highlighting pre-clinical data from the CoStAR platform which demonstrated that CoStAR expression by T cells led to marked enhancement of effector function and proliferation of T cells and TILs. The novel design of CoStAR, which includes two intracellular costimulatory domains derived from CD28 and CD40, showed significantly improved activity compared to a CoStAR that contained only a CD28 domain, demonstrating the superiority of CD40-containing CoStAR molecules and important synergies of CD40 and CD28 signaling. Further details can be found in the poster publications available here.
Third Quarter 2021 Financial and Operating Results:

As of September 30, 2021, we had $20.4 million in cash and cash equivalents and $495.0 million in marketable securities, compared to $241.7 million in cash and cash equivalents and no investments in marketable securities as of December 31, 2020. The Company expects that its cash, cash equivalents and marketable securities as of September 30, 2021 will enable it to fund its operating plan into 2023.

Research and development expenses were $29.1 million and $64.7 million for the three and nine months ended September 30, 2021, compared to $4.9 million and $9.2 million for the three and nine months ended September 30, 2020.

General and administrative expenses were $14.0 million and $37.1 million for the three and nine months ended September 30, 2021, compared to $2.9 million and $7.2 million for the three and nine months ended September 30, 2020.

On November 15, 2021 Instil Bio, Inc. ("Instil") (Nasdaq: TIL), a clinical-stage biopharmaceutical company focused on developing tumor infiltrating lymphocyte, or TIL, therapies for the treatment of patients with cancer, reported poster presentations demonstrating pre-clinical data of the CoStimulatory Antigen Receptor (CoStAR) platform at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) (SITC 2021), held from November 10-14, 2021 (Press release, Instil Bio, NOV 15, 2021, View Source [SID1234595616]). Instil also presented a Trials-in-Progress poster detailing DELTA-1, the ongoing Phase 2 study of ITIL-168 in advanced melanoma.

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Pre-clinical data of the anti-FOLR1 CoStAR construct utilized in ITIL-306, Instil’s first genetically-engineered CoStAR-TIL product candidate, was shown in Poster 198. The results demonstrated that CoStAR broadly enhances effector function of T cells including cytolytic activity, cytokine secretion and proliferation of T cells. CoStAR did not stimulate T cells on its own, but only increased T-cell function in the presence of signals activating both the tumor-reactive TCR and the CoStAR molecule. Additionally, data were presented that showed CoStAR was transduced at high efficiency (greater than 40%) into primary ovarian cancer TILs and effector function of CoStAR-TIL was increased over untransduced TILs when cocultured with autologous tumor cells.

The proprietary CoStAR platform utilizes intracellular CD28 and CD40 domains to deliver novel synergistic costimulatory activity to T cells. Poster 199 showcased enhanced activity of T cells engineered with dual CD28/CD40-containing CoStARs, with greater proliferation, enhanced effector function, and a superior cytokine secretion profile compared to a CD28-only CoStAR. Importantly, CoStAR-expressing T cells proliferated exponentially after exposure to tumor antigen, even in the absence of exogenous interleukin (IL)-2, a key required growth factor for T cells in vitro.

"These data further support our excitement for the CoStAR platform, which addresses a major challenge for solid tumor cell therapy: the lack of effective costimulation within the tumor microenvironment," said Mark Dudley, Ph.D., Head of Research at Instil. "The optimized intracellular signaling domains of our CoStAR platform include CD28 and CD40, which demonstrate superior performance over CoStARs containing only CD28."

"With the encouraging preclinical data presented at SITC (Free SITC Whitepaper), we are optimistic that CoStAR may be able to enhance the activity of TILs in patients with cancer and may eliminate the need for high doses of post-infusion IL-2, which is a frequent cause of toxicity in unmodified TIL therapy," said Zachary Roberts, M.D. Ph.D., Chief Medical Officer of Instil Bio. "We continue to look forward to the upcoming Phase 1 first-in-human study of ITIL-306 which we expect to initiate in the first half of 2022."

The company also presented a trial-in-progress poster for DELTA-1, the ongoing Phase 2 study of ITIL-168 in advanced melanoma (Poster 544).

Details of the poster presentations are as follows:

Title: Costimulatory antigen receptor (CoStAR): a novel platform that enhances the activity of TILs
Authors: Sukumaran S, et al.
Poster/Abstract Number: 198 / DOI: 10.1136/jitc-2021-SITC2021.198

Title: Potent T cell costimulation mediated by a novel costimulatory antigen receptor (CoStAR) with dual CD28/CD40 signaling domains to improve adoptive cell therapies
Authors: Sykorova M, et al.
Poster/Abstract Number: 199 / DOI: 10.1136/jitc-2021-SITC2021.199

Title: A global, multicenter phase 2 study of ITIL-168, an unrestricted autologous TIL cell therapy, in adult patients with advanced cutaneous melanoma
Authors: Gastman B, et al.
Poster/Abstract Number: 544 / DOI: 10.1136/jitc-2021-SITC2021.544

The posters are available on the publications section of the Instil Bio website: www.instilbio.com/publications.

About CoStAR

CoStAR (Co-Stimulatory Antigen Receptor) is a novel platform technology used to create a new class of genetically engineered TIL therapies. These modified TILs rely on their native, patient-specific T cell receptors, or TCRs, for detection of tumor-specific antigens, with significantly enhanced effector function when the CoStAR molecule is simultaneously bound to its target in the tumor microenvironment. Submission of the IND for ITIL-306, Instil’s lead CoStAR-TIL product candidate which binds FOLR1 (Folate Receptor Alpha), is anticipated for the first half of 2022.

About ITIL-168

ITIL-168 is an investigational, autologous cell therapy made from tumor infiltrating lymphocytes, or TILs. Made from each patient’s digested and cryopreserved tumor, ITIL-168 is a TIL cell therapy manufactured to offer an unrestricted T cell receptor (TCR) repertoire. Instil’s proprietary, optimized, and scalable manufacturing process has been designed to capture and preserve the maximum diversity of each patient’s TILs. By collecting the patient’s tumor and immediately processing and then cryopreserving it, our process offers significant scheduling flexibility for patients and physicians at the time of both tumor resection and TIL treatment. In addition to DELTA-1, Instil plans to investigate ITIL-168 in additional solid tumor indications in Phase 1 clinical trials beginning in 2022.

About DELTA-1

DELTA-1 is a global, multicenter Phase 2 clinical trial of ITIL-168 in adult patients with advanced melanoma. Using an open-label, single-arm design, the main study cohort will evaluate the efficacy and safety of ITIL-168, when administered after a 5-day course of lymphodepleting chemotherapy and followed by up to 8 doses of high-dose interleukin-2 (IL-2), in patients whose cancer has progressed following a PD-1 inhibitor and, if positive for a BRAF-activating mutation, a BRAF inhibitor. Approximately 80 subjects are planned for enrollment and treatment in Cohort 1. Cohort 2 is anticipated to enroll approximately 25 subjects and is designed to evaluate the efficacy and safety of the regimen in patients who required discontinuation of PD-1 inhibitor(s) due to unacceptable toxicity, regardless of best overall disease response. Cohort 3 is also anticipated to enroll approximately 25 subjects and will evaluate efficacy and safety in patients whose best ongoing response to PD-1 inhibitor(s) is stable disease. Patients in Cohorts 2 and 3 whose cancer expresses a BRAF-activating mutation will be required to have experienced disease progression following BRAF inhibitor therapy. The primary endpoint of DELTA-1 is the objective response rate (ORR) according to RECIST v1.1 as assessed by independent central review. Secondary endpoints include disease control rate, duration of response, progression-free survival, overall survival, and safety.