On November 8, 2023 Invitae (NYSE: NVTA), a leading medical genetics company, reported results for the third quarter ended September 30, 2023 (Press release, Invitae, NOV 8, 2023, View Source [SID1234637260]).

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"The Company executed well on key operating and financial metrics in the third quarter, and remains on track to meet or beat annual guidance," said Ken Knight, president and chief executive officer of Invitae. "On the operational front, we added key executive talent and achieved a number of clinical milestones that should strengthen the health of our business, deliver continuing market expansion and further differentiate our testing portfolio from competitors."

Third Quarter 2023 Financial Results

Third quarter revenue decreased 9% to $121.2 million compared to $133.5 million in the same period in the prior year, primarily reflecting the impact of exited businesses and geographies completed in 2022. After adjusting for revenue of $17.2 million in the prior year period related to the discontinued businesses, third quarter revenue increased approximately 4% on a pro forma basis, with U.S. hereditary cancer testing volume achieving double-digit percentage growth compared to the prior year period.
Gross profit was $39.1 million in the quarter, compared with $16.6 million in the same period of 2022, or 135.6% year-over-year growth. Non-GAAP gross profit was $63.6 million in the quarter, compared with $61.2 million in the third quarter of 2022, representing a year-over-year growth rate of 3.8%.
Gross margin was 32.2% in the third quarter, compared with 12.4% a year ago. Non-GAAP gross margin was 52.4% compared with 45.9% in the third quarter of 2022. This represents Invitae’s ninth consecutive quarter of non-GAAP gross margin improvement.
Operating expense for the third quarter of 2023 was $1.0 billion, compared with $306.5 million in the third quarter of 2022. Operating expense in the third quarter includes $877.3 million in restructuring, impairment and other costs primarily related to an impairment charge of the Company’s long-lived assets, compared with $125.2 million in the prior year period. Non-GAAP operating expense was $122.1 million for the third quarter of 2023, compared with $150.0 million for the third quarter of 2022. Non-GAAP operating expense as a percentage of revenue was 101%, compared with 112% in the third quarter of 2022.
As of September 30, 2023, Invitae had $264.7 million of cash, cash equivalents, restricted cash and marketable securities compared to $557.1 million as of December 31, 2022.
Net decrease in cash, cash equivalents, restricted cash and net changes in investments in the quarter was $72.2 million. Cash burn in the quarter was $64.1 million.
Total patients served as of September 30, 2023 was approximately 4.4 million with 64% available for data sharing.
Third quarter net loss per basic and diluted share of ($3.42) included impairment and losses on disposals of long-lived assets, net, employee severance and benefits and other restructuring costs of $877.3 million primarily related to fair market value assessment of the Company’s intangible assets. Third quarter non-GAAP net loss per basic and diluted share of ($0.10) excludes this charge. Compared to a year ago, net loss per basic and diluted share and non-GAAP net loss per basic and diluted share were ($1.27) and ($0.42), respectively.
Operational improvement efforts and expense control have resulted in margin expansion and stronger financial performance. In addition, the Company is engaging with stakeholders to strengthen the balance sheet, and the Board of Directors has formed a special committee focused on improving the Company’s capital structure. The Company is exploring a number of options, including, but not limited to, raising capital, asset sales, business and R&D refocusing efforts, capital expenditure and operating expense reductions and addressing its debt obligations.

Reaffirming Fiscal 2023 Outlook

For the full year, Invitae is reaffirming its fiscal 2023 outlook. The Company expects revenue in the range of $480-$500 million and non-GAAP gross margin in the range of 48-50%.

Ongoing cash burn includes cash, cash equivalents, marketable securities and restricted cash and excludes certain items. The Company continues to expect ongoing cash burn to be in the range of $220-$245 million in 2023. In 2023, cash burn will be higher than ongoing cash burn as a result of the Company’s voluntary repayment of its $135 million term loan in the first quarter of 2023.

Webcast and Conference Call Details

Management will host a conference call and webcast today at 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time to discuss financial results and recent developments. To access the conference call, please register at the link below:

View Source;confId=56925

Upon registering, each participant will be provided with call details and access codes.

The live webcast of the call and slide deck may be accessed here or by visiting the investors section of the company’s website at ir.invitae.com. A replay of the webcast will be available shortly after the conclusion of the call and will be archived on the company’s website.

On November 8, 2023 Immatics N.V. (NASDAQ: IMTX, "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported interim data from the ongoing Phase 1 trial with ACTengine IMA203 in patients with recurrent and/or refractory solid cancers (Press release, Immatics, NOV 8, 2023, View Source [SID1234637259]). The update is focused on IMA203 GEN1 in melanoma at the recently defined recommended Phase 2 dose (RP2D) and the first clinical data for IMA203CD8 GEN2.

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Treatment with IMA203 GEN1 monotherapy in Phase 1a and Phase 1b Cohort A at RP2D demonstrated durable objective responses in melanoma patients with one patient exceeding 12 months and two patients exceeding 15 months post infusion and a 50% (6/12) confirmed objective response rate (cORR). In line with previous results, IMA203 GEN1 monotherapy was well tolerated at total doses up to 10×109 TCR-T cells infused.

In addition, the first data on the company’s second-generation product candidate IMA203CD8 demonstrated 56% (5/9) cORR with enhanced pharmacology and a differentiated response pattern compared to IMA203 GEN1. The company plans to develop IMA203 GEN1 in melanoma and to pursue development of IMA203 in ovarian cancer, uterine cancer, NSCLC, triple-negative breast cancer and other tumor types preferentially with IMA203CD8 GEN2.

The melanoma-focused data on IMA203 GEN1 will be presented today by Martin Wermke, MD, Professor at the University Hospital Dresden and Coordinating Investigator of the ACTengine IMA203 TCR-T trial, at the 20th International Congress of the Society for Melanoma Research in Philadelphia, PA, taking place November 6th-9th, 2023.

In addition, Dr. Wermke together with Cedrik Britten, MD, Chief Medical Officer at Immatics will provide the complete data update during a conference call and webcast today, November 8 at 8:30 am EST/2:30 pm CET. The presentation is available on Immatics’ website – covering the complete data set including Phase 1a, Phase 1b Cohort A and the deprioritized Cohort B (IMA203 GEN1 combined with nivolumab).

"A cancer diagnosis can be the start of a daunting journey characterized by devastating setbacks when conventional therapies fail. I believe that the updated data on IMA203 GEN1 shows meaningful benefit and long-term durability in melanoma patients," said Martin Wermke, MD, Coordinating Investigator of the ACTengine IMA203 TCR-T trial. "With the maturation of the clinical data set, it becomes progressively evident for me that targeting PRAME with Immatics’ IMA203 TCR-T approach has the potential to provide a durable benefit for advanced-stage checkpoint- and BRAF-inhibitor refractory melanoma patients."

"Today, we are excited to report on the continued clinical progress for our ACTengine IMA203 TCR-T cell therapies, which we believe have demonstrated meaningful clinical benefit for last-line solid cancer patients treated with IMA203 or its second-generation product candidate IMA203CD8. We now plan to progress IMA203 into a registration-enabling Phase 2 trial in melanoma as quickly as possible, while we believe that our second-generation approach is exhibiting unique patterns in pharmacology guiding our development efforts towards other tumor types such as ovarian, uterine, lung and triple-negative breast cancer", commented Dr. Cedrik Britten, Chief Medical Officer at Immatics. "We plan to provide an update on the clinical development plan for IMA203 in the first quarter of 2024 as well as updates across the entire clinical TCR cell therapy and bispecifics portfolio throughout 2024."

Clinical data on anti-tumor activity and safety

IMA203 GEN1 in melanoma patients treated at RP2D: IMA203 GEN1 demonstrates a high rate of objective responses with ongoing durability of more than 15 months after treatment

At data cut-off on September 30, 2023, a total of 16 PRAME-positive patients with cutaneous, uveal or melanoma of unknown primary origin were infused with IMA203 GEN1 at the recommended Phase 2 dose (RP2D, 1-10×109 total TCR-T cells) across Phase 1a or Phase 1b Cohort A.
IMA203 GEN1 monotherapy continues to be well tolerated. All 16 patients experienced cytopenia (Grade 1-4) associated with lymphodepletion as expected. Patients had mostly mild-moderate cytokine release syndrome (CRS), of which 10 patients (63%) had Grade 1, and 5 patients (31%) Grade 2 and 1 patient (6%) Grade 3 CRS. One non-serious, mild (Grade 1) immune effector cell associated neurotoxicity syndrome (ICANS) was observed. No dose-dependent increase of CRS, no dose-limiting toxicities (DLTs) and no IMA203-related death was observed. The safety profile for non-melanoma patients treated with IMA203 GEN1 was generally consistent with safety in the melanoma subset and is provided in the appendix of the presentation.
13 out of 16 infused patients were evaluable for efficacy analysis based on at least one tumor response assessment being available post treatment. These patients received a median total infused dose of 1.73×109 IMA203 TCR-T cells (range 1.07-5.12×109 TCR-T cells).
Most patients were heavily pre-treated with a median of 4 lines of systemic therapies, thereof a median of 2 lines of checkpoint inhibitors; all 8 cutaneous melanoma patients were checkpoint inhibitor-refractory and 5 of 8 were BRAF inhibitor-pretreated.
50% (6/12) confirmed objective response rate (cORR) and 62% (8/13) initial ORR (RECIST 1.1).
Durability of responses ongoing beyond 12 months in one patient and 15 months in two patients after treatment.
Median duration of response (mDOR) was not reached (min 2.2+ months, max 14.7+ months) at a median follow-up (mFU) of 14.4 months.
RP2D has been defined at 1-10×109 total TCR-T cells.
Cell product manufacturing:
7-day manufacturing process plus 7-day release testing
Manufacturing success rate: >95% to reach RP2D
Immatics has recently received Regenerative Medicine Advanced Therapy (RMAT) designation from the FDA for IMA203 GEN1 in multiple PRAME-expressing cancers, including cutaneous and uveal melanoma, and is now targeting a registration-enabling Phase 2 trial in cutaneous melanoma potentially bundled with uveal melanoma in 2024. Discussions with FDA to align on patient populations, trial design and CMC aspects concerning the planned Phase 2 trial are ongoing.
IMA203CD8 GEN2 in Cohort C: First clinical data set on IMA203CD8 shows an enhanced pharmacology profile with a differentiated response pattern compared to IMA203 GEN1

At data cut-off on September 30, 2023, a total of 12 PRAME-positive patients were infused with IMA203CD8 GEN2 across DL3 (0.2-0.48×109 TCR-T cells/m2 BSA), DL4a (0.481-0.8×109 TCR-T cells/m2 BSA) and DL4b (0.801-1.2×109 TCR-T cells/m2) in Cohort C with a median total infused dose of 1.17×109 IMA203CD8 TCR-T cells (range 0.64-2.05×109 TCR-T cells).
All patients were heavily pre-treated with a median of 3 lines of systemic therapies.
All patients experienced cytopenia (Grade 1-4) associated with lymphodepletion as expected. 11 out of 12 patients (92%) experienced a cytokine release syndrome (CRS), of which 8 patients (67%) had Grade 1 or 2 CRS, 2 patients (17%) had Grade 3 CRS and 1 patient (8%) had a Grade 4 CRS. The latter patient also had a reported Grade 4 neurotoxicity. No ICANS or neurotoxicity was reported for the other patients. No IMA203CD8-related deaths were observed. Dose-limiting toxicities (DLTs) were reported for 2 of 4 patients treated at DL4b. No DLT was reported for all 4 patients treated at DL3, or all 4 patients treated at DL4a. DL4a dose cohort is ongoing.
Initial clinical activity was observed with a cORR of 56% (5/9) and initial ORR of 58% (7/12) (RECIST 1.1).
6 of 7 responses (including two unconfirmed responses with no subsequent scan available at data cut-off) were ongoing at data cut-off with longest response at >12 months after infusion.
mDOR was not reached (min 2.0+ months, max 11.5+ months) at a mFU of 4.8 months.
Reduction of tumor size was observed in 11 out of 12 patients, with a deepening of response from initially stable disease (SD) to partial response (PR) observed in two patients.
Translational data showed enhanced pharmacology of IMA203CD8 GEN2: trend towards responses at lower T cell dose and higher tumor burden compared to IMA203 GEN1; IMA203CD8 GEN2 achieved higher peak expansion (Cmax) when normalized to infused dose and T cells showed higher initial activation levels without exhaustion over time.
Overview of patient characteristics and anti-tumor activity across IMA203 clinical trial cohorts

IMA203 GEN1 IMA203CD8 GEN2
All Comers
(N=45) Melanoma Subgroup
(N=13 out of 45) All Comers
(N=12)
Phase 1a Cohort A Phase 1a + Cohort A Cohort C
Efficacy population* N=27
Thereof N=7 at RP2D N=18 at RP2D N=13 at RP2D N=12
Dose level DL1-4 DL4/5 DL4/5 DL3/DL4a/DL4b
ORR 48%
(13/27) 50%
(9/18) 62%
(8/13) 58%
(7/12)
cORR 19%
(5/27) 47%
(8/17) 50%
(6/12) 56%
(5/9)
mDOR [months] 4.4
(2.4, 23.0) Not reached Not reached Not reached
mFU [months] Not defined# 10.8 14.4 4.8
* Patients with at least one available tumor response assessment post infusion; # All patients were PD at data cut-off; Initial ORR: Objective response rate according to RECIST 1.1 at any post infusion scan; Confirmed ORR (cORR): Confirmed objective response rate according to RECIST 1.1 for patients with at least two available post infusion scans or patients with progressive disease (PD) at any prior timepoint, patients with ongoing unconfirmed PR not included in cORR calculation; Duration of response (DOR) in confirmed responders is defined as time from first documented response until disease progression/death. Patients with ongoing response will be censored at date of data cut-off. Median DOR (mDOR) is analyzed by using the Kaplan-Meier method; Median Follow-up (mFU) is analyzed by using the reverse Kaplan-Meier method.

The full data analysis including IMA203 GEN1 in Phase 1a and Cohort A as well as deprioritized Cohort B (IMA203 in combination with a checkpoint inhibitor), is available as part of the presentation on the company’s website.

Development path for IMA203 GEN1 and IMA203CD8 GEN2 monotherapies
The goal of Immatics’ development strategy is to make its cell therapies targeting PRAME available to the broadest possible solid cancer patient population with an initial focus on the US market. To achieve this, Immatics has announced a three-step development strategy for leveraging the full breadth of PRAME, a target that is highly expressed in various solid cancers.

Focus on IMA203 GEN1 in cutaneous melanoma (potentially bundled with uveal melanoma), targeted to enter a registration-enabling Phase 2 clinical trial in 2024. Discussions with FDA to align on patient population, clinical trial design and CMC aspects are ongoing under the RMAT designation achieved for IMA203 GEN1 in multiple cancer types including cutaneous and uveal melanoma. There are up to 3,300 HLA-A*02 and PRAME-positive cutaneous and uveal melanoma last-line patients per year in the US. A next update on the clinical development plan is expected in the first quarter of 2024.

In parallel, commence dedicated dose expansion cohorts for signal finding in ovarian and uterine cancer, preferentially with IMA203CD8 GEN2. Enrollment of patients with these cancer types is already ongoing. There are up to 9,000 HLA-A*02 and PRAME-positive ovarian and uterine last-line cancer patients per year in the US.

The development of a broader tumor-agnostic label in PRAME+ solid cancers, including in NSCLC, triple-negative breast cancer, and others. This could leverage the full potential of PRAME across multiple solid cancer types.

Immatics conference call and webcast
Immatics will host a conference call and webcast today, November 8, 2023, at 8:30 am EST/2:30 pm CET to discuss the clinical data. The presentation can be accessed directly through this link. A replay of the webcast will be made available shortly after the conclusion of the call and archived on the Immatics website for at least 90 days.

About IMA203 and target PRAME
ACTengine IMA203 T cells are directed against an HLA-A*02-presented peptide derived from preferentially expressed antigen in melanoma (PRAME), a protein frequently expressed in a large variety of solid cancers, thereby supporting the program’s potential to address a broad cancer patient population. Immatics’ PRAME peptide is present at a high copy number per tumor cell and is homogeneously and specifically expressed in tumor tissue. The peptide has been identified and characterized by Immatics’ proprietary mass spectrometry-based target discovery platform, XPRESIDENT. Through its proprietary TCR discovery and engineering platform XCEPTOR, Immatics has generated a highly specific T cell receptor (TCR) against this target for its TCR-based cell therapy approach, ACTengine IMA203.

ACTengine IMA203 TCR-T is currently being evaluated in Phase 1 Cohort A IMA203 GEN1 monotherapy, and Cohort C IMA203CD8 GEN2 monotherapy, where IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor. As previously reported, Cohort B IMA203 in combination with an immune checkpoint inhibitor has been deprioritized.

About ACTengine
ACTengine is a personalized cell therapy approach for patients with advanced solid tumors. The patient’s own T cells are genetically engineered to express a novel, proprietary TCR directed against a defined cancer target. The modified T cells are then reinfused into the patient to attack the tumor. The approach is also known as TCR-engineered cell therapy (TCR-T). All Immatics’ ACTengine product candidates are manufactured utilizing a proprietary manufacturing process designed to enhance T cell engraftment and persistence in vivo.

The ACTengine T cell products are manufactured at the Evelyn H. Griffin Stem Cell Therapeutics Research Laboratory in collaboration with UTHealth.

On November 8, 2023 Gritstone bio, Inc. (Nasdaq: GRTS), a clinical-stage biotechnology company working to develop the world’s most potent vaccines, reported financial results for the third quarter ended September 30, 2023 and provided recent corporate and clinical updates (Press release, Gritstone Bio, NOV 8, 2023, View Source [SID1234637258]).

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"As cancer and infectious diseases continue to challenge human health across the globe, we at Gritstone continue advancing our vision to deliver more potent and durable vaccines," said Andrew Allen, M.D., Ph.D., Co-founder, President, and Chief Executive Officer of Gritstone bio. "The ongoing advancement of our CORAL program positions our infectious disease approach, which combines self-amplifying mRNA (samRNA) with novel B and T cell targets, as a leading potential next-generation vaccine platform for COVID-19 and beyond. We believe the data recently shared at IDWeek underscore the promise of this novel approach to drive broad and long-lasting clinical protection against COVID-19 with vaccine-elicited neutralizing antibodies against the virus persisting at high concentrations for at least 12 months, unlike current approved vaccines. In oncology, preliminary findings from the randomized Phase 2/3 study of our personalized cancer vaccine, GRANITE, in MSS-CRC are rapidly approaching. This is important data not only for Gritstone but for the field, as GRANITE represents an opportunity to bring a new class of therapy to patients with ‘cold’ solid tumors, for whom the benefits of today’s immunotherapies are minimal. The scientific bedrock of GRANITE extends to SLATE, where our collaboration with Steven A. Rosenberg and the NCI is now advancing. With GRANITE and CORAL now in or entering randomized Phase 2 studies, Gritstone stands at the precipice of unlocking the full potential of our novel vaccine platforms in both oncology and infectious diseases."

Corporate Update

•
In August 2023, Gritstone and Genevant Sciences entered into a multi-year option and license agreement that provides Gritstone with nonexclusive access to Genevant’s leading LNP technology, on a pathogen-by-pathogen basis, for development and commercialization of Gritstone’s samRNA infectious disease vaccines.

Clinical Program Updates

Tumor-Specific Neoantigen Oncology Programs (GRANITE and SLATE)

GRANITE – Personalized neoantigen vaccine program
SLATE – "Off-the-shelf" neoantigen vaccine program

•
The Phase 2 portion of the Phase 2/3 study evaluating GRANITE as a maintenance therapy in first-line MSS-CRC remains ongoing, and preliminary efficacy data from the Phase 2 portion remain expected in the first quarter of 2024. Gritstone met its enrollment target of 100 patients randomized in August 2023.
•
The clinical trial collaboration with the National Cancer Institute (NCI) to evaluate an autologous T cell therapy in combination with Gritstone’s KRAS-directed "off the shelf" vaccine candidate, SLATE-KRAS, is ongoing. An IND to run a Phase 1 study was cleared by the U.S. Food and Drug Administration (FDA) in October 2023. The study is led by Steven A. Rosenberg, M.D., Ph.D., Chief of the Surgery Branch at the NCI’s Center for Cancer Research. Under the terms of the collaboration, Gritstone will provide the SLATE-KRAS vaccine as requested by NCI. NCI will be responsible for conducting the study at the NIH Clinical Center.
•
Gritstone intends to initiate a randomized Phase 2 clinical trial within SLATE ("off-the-shelf" neoantigen vaccine program) in 2024.

Infectious Disease Programs

CORAL – Next-generation SARS-CoV-2 vaccine program that serves as proof-of-concept for Gritstone’s samRNA platform and novel approach in infectious diseases

•
In September 2023, Gritstone was awarded a contract by BARDA (the Biomedical Advanced Research and Development Authority), part of the Administration for Strategic Preparedness and Response in the U.S. Department of Health and Human Services, to conduct a Phase 2b comparative study evaluating its next-generation vaccine candidate against COVID-19(a). Per the contract, which is valued at up to $433.0 million, Gritstone is currently preparing to conduct a 10,000 participant, randomized Phase 2b double-blinded study to compare the efficacy, safety, and immunogenicity of Gritstone’s samRNA vaccine candidate against an approved COVID-19 vaccine. Preparations for the study are covered under the initial base period of the contract. Gritstone expects the study to be initiated in the first quarter of 2024.
•
In October 2023, new data was presented from Gritstone’s three Phase 1 CORAL studies. Results across these studies highlighted the potential of Gritstone’s next-generation samRNA-based approach, which incorporates Spike plus other viral targets ("Spike plus"), to drive broad and long-lasting clinical protection against COVID-19. Highlights from the data, which were presented at IDWeek 2023, include:
o
High neutralizing antibody (nAb) responses were sustained through the latest evaluable timepoints across all three studies, highlighting potential for durable clinical protection.
▪
High nAb levels were demonstrated through at least 12 months in the CORAL-CEPI and CORAL-BOOST studies and at least 6 months in the CORAL-NIH study.
o
T cell responses to Spike plus other viral targets observed in all Phase 1 studies, demonstrating broad and potentially variant-proof immune response.
o
Vaccine candidates were generally well tolerated in all Phase 1 studies; over 300 subjects dosed to date. See all poster presentations here: CORAL-CEPI, CORAL-BOOST, CORAL-NIH

HIV – Collaboration with Gilead under Gilead’s HIV Cure Program to research and develop vaccine-based HIV immunotherapy treatment

•
The collaboration with Gilead to research and develop a vaccine-based HIV immunotherapy treatment remains active and ongoing.

Third Quarter 2023 Financial Results

•
Cash, cash equivalents, marketable securities and restricted cash were $90.5 million as of September 30, 2023, compared to $185.2 million as of December 31, 2022.

•
Research and development expenses were $32.8 million for the three months ended September 30, 2023, compared to $26.4 million for the three months ended September 30, 2022. The increase of $6.3 million was primarily due increases of $2.5 million in milestone and license payments, $1.0 million in personnel-related expenses, $2.0 million in facilities-related costs, and $0.9 million in outside services, consisting primarily of clinical trial and other chemistry, manufacturing and controls-related expenses, offset by decreases of $0.1 million in laboratory supplies.

•
General and administrative expenses were $7.4 million for the three months ended September 30, 2023, compared to $6.5 million for the three months ended September 30, 2022. The increase of $0.9 million was primarily due to increases of $0.5 million in outside services, $0.2 million in personnel-related expenses, and $0.2 million in facilities-related costs.

•
Collaboration, license, and grant revenues were $1.6 million for the three months ended September 30, 2023, compared to $3.0 million for the three months ended September 30, 2022. During the three months ended September 30, 2023, we recorded $0.1 million in collaboration revenue related to the Gilead collaboration agreement, $0.3 million in collaboration revenue related to the 2seventy agreement, $0.8 million in grant revenue from the CEPI funding agreement, and $0.4 million in grant revenue pursuant to the Gates grant agreement.

On November 8, 2023 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a first-in-class pipeline of induced pluripotent stem cell (iPSC)-derived cellular immunotherapies to patients with cancer and autoimmune disorders, reported business highlights and financial results for the third quarter ended September 30, 2023 (Press release, Fate Therapeutics, NOV 8, 2023, View Source [SID1234637257]).

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"We achieved several key milestones for our iPSC product platform in oncology and autoimmunity, creating additional opportunities to generate new clinical data across multiple programs during 2024," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We have initiated patient enrollment in our Phase 1 study of FT522, our ADR-armed, CD19-targeted CAR NK cell program, where we intend to assess FT522 with and without conditioning chemotherapy in patients with B-cell lymphoma. In addition, our IND application was cleared by the FDA for FT825/ONO-8250 in solid tumors under our collaboration with ONO Pharmaceutical, which multiplexed-engineered CAR T-cell program incorporates seven synthetic controls of cell function including a novel cancer-specific binding domain targeting HER2. Finally, I am pleased to announce the expansion of our iPSC product platform into autoimmunity with the clearance by the FDA of our IND application for FT819, our off-the-shelf, CD19-targeted CAR T-cell program, in systemic lupus erythematosus."

FT522 iPSC-derived CAR NK Cell Program in B-cell Lymphoma

Phase 1 Study of ADR-armed, CD19-targeted CAR NK Cell Program Open for Enrollment. FT522 is the Company’s off-the-shelf, multiplexed-engineered natural killer (NK) cell product candidate that incorporates five synthetic controls of cell function. It is the Company’s first product candidate armed with its proprietary alloimmune defense receptor (ADR) technology, which is comprised of a synthetic engineered receptor targeting 4-1BB expressed on alloreactive immune cells. In preclinical studies, engagement of ADR-armed CAR NK cells with alloreactive immune cells mitigated rejection, promoted cellular proliferation, and increased anti-tumor activity, indicating that ADR-armed CAR NK cells may be effective without requiring administration of intensive conditioning chemotherapy to patients. The Phase 1 study of FT522 in combination with rituximab for relapsed / refractory B-cell lymphoma (BCL) is designed to assess safety, pharmacokinetics, and activity with and without administration of a standard three-day preconditioning regimen to patients. Enrollment into the first three-dose cohort at 300 million cells per dose has been initiated. The Company is also assessing in preclinical studies the potential of FT522 to induce benefit across a range of autoimmune diseases.

FT825/ONO-8250 iPSC-derived CAR T-cell Program in Solid Tumors

IND Application Cleared by FDA for Multiplexed-engineered, CAR T-cell Program Incorporating Seven Novel Synthetic Controls of Cell Function. Under the Company’s collaboration with ONO Pharmaceutical Co., Ltd. (ONO), the companies are co-developing FT825/ONO-8250, an iPSC-derived CAR T-cell product candidate that incorporates a novel cancer-specific H2CasMab-2 CAR targeting HER2 and is designed to overcome unique challenges in treating solid tumors. The Company’s Investigational New Drug (IND) application for FT825/ONO-8250 was cleared by the U.S. Food and Drug Administration (FDA) in October for conduct of a Phase 1 study in patients with advanced solid tumors. The dose-escalation schema includes two treatment regimens: single-dose FT825/ONO-8250 as monotherapy; and FT825/ONO-8250 in combination with cetuximab. Novel synthetic controls incorporated into the multiplexed-engineered CAR T-cell product candidate include a CXCR2 receptor to promote cell trafficking, a chimeric TGFβ receptor to redirect immunosuppressive signals in the tumor microenvironment, and a high-affinity, non-cleavable CD16a receptor to promote antibody-dependent cellular cytotoxicity. Preclinical data of FT825/ONO-8250, which was presented at the 2023 Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) Annual Meeting, demonstrated that the antigen binding profile of H2CasMab-2 is unique and differentiated from that of trastuzumab, exhibiting similar potency with greater specificity for malignant HER2-expressing cells.

FT819 iPSC-derived CAR T-cell Program in Systemic Lupus Erythematosus and B-cell Malignancies

Expansion into Autoimmunity with Phase 1 Study Start-up Ongoing in SLE. In July, the Company’s IND application was cleared by the FDA for clinical investigation of FT819 in patients with systemic lupus erythematosus (SLE), including those with active lupus nephritis (LN) or active SLE without renal involvement. FT819 is the Company’s off-the-shelf, iPSC-derived CAR T-cell product candidate that incorporates several novel synthetic controls of cell function including the integration of a novel CD19-targeted 1XX CAR construct into the T-cell receptor alpha constant (TRAC) locus, which is intended to promote uniform CAR expression, enhance T-cell potency, and prevent graft-versus-host disease. The clinical trial is designed to evaluate the safety, pharmacokinetics, anti-B-cell activity of a single dose of FT819 administered following a standard three-day preconditioning regimen. The FT819 Phase 1 protocol received a favorable review by clinical experts of the Protocol Design Committee of Lupus Therapeutics, an affiliate of the Lupus Research Alliance.

Phase 1 Study Advancing in Single-dose Escalation Cohorts for B-cell Malignancies. The Company’s landmark Phase 1 clinical trial of FT819 is the first-ever clinical investigation of a T-cell product candidate manufactured from a clonal master iPSC line. The Company is currently enrolling patients in single-dose treatment cohorts at 540 million cells in BCL and at 360 million cells in chronic lymphocytic leukemia using a standard three-day preconditioning regimen. Clinical data previously presented by the Company from the first 11 patients with relapsed / refractory BCL treated with a single dose of FT819 at up to 360 million cells showed anti-tumor activity including three complete responses and one partial response, CAR T-cell expansion that peaked in the peripheral blood between Days 8 and 11, and a favorable safety profile with no immune effector-cell associated neurotoxicity syndrome (ICANS) and mild cytokine release syndrome (CRS).

FT576 iPSC-derived CAR NK Cell Program in Multiple Myeloma

Phase 1 Study Accruing Patients in Three-dose Treatment Cohorts. The Company’s Phase 1 study of FT576, its multiplexed-engineered BCMA-targeted CAR NK cell product candidate for relapsed / refractory multiple myeloma, is currently enrolling patients in two, three-dose treatment cohorts at 1 billion cells per dose. The Company has treated three patients as monotherapy as well as two patients in combination with CD38-targeted monoclonal antibody therapy to assess the therapeutic potential of dual-antigen targeting of myeloma cells, with no dose-limiting toxicities reported by investigators in either cohort.

Third Quarter 2023 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of September 30, 2023 were $349.7 million. In addition, as of September 30, 2023, cash receivables from the Company’s collaboration with ONO were $1.5 million.
Total Revenue: Revenue was $1.9 million for the third quarter of 2023, which was derived from the Company’s conduct of preclinical development activities for a second collaboration candidate targeting an undisclosed solid tumor antigen under its collaboration with ONO.
Total Operating Expenses: For the third quarter of 2023, GAAP operating expenses were $53.2 million, including research and development expenses of $34.3 million and general and administrative expenses of $18.9 million. Such amounts included $10.1 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 98.6 million, and preferred shares outstanding were 2.8 million, as of September 30, 2023. Each preferred share is convertible into five common shares.

Today’s Conference Call and Webcast

The Company will conduct a conference call today, Wednesday, November 8, 2023 at 5:00 p.m. ET to review financial and operating results for the quarter ended September 30, 2023. In order to participate in the conference call, please register using the conference link here. The live webcast can be accessed under "Events & Presentations" in the Investors section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

On November 8, 2023 Evotec SE (Frankfurt Stock Exchange: EVT, MDAX/TecDAX, ISIN: DE0005664809; NASDAQ: EVO) reported the financial results and corporate updates for the first nine months 2023 (Press release, Evotec, NOV 8, 2023, View Source [SID1234637256]).

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HIGHLIGHTS

EVOTEC’S TOPLINE SUCCESS REFLECTS STRONG DEMAND

Group revenues increased by 14% (19% excluding fx-effects) to € 580.1 m (9M 2022: € 510.8 m); excluding a lower contribution from milestones, upfronts and license payments, Base business at € 575.3 m (9M 2022: € 502.8 m) continued to show comparable growth of 14%.
Costs of € 43.9 m were incurred in 2023 as a direct result of the cyber-incident in early April, including additional external expenditures and internal recovery contributions.
Total EVT Execute revenues (incl. intersegment revenues) up 3% to € 543.4 m (9M 2022: € 526.7 m), strongly affected by cyber-incident; EVT Innovate revenues up 64% to € 199.9 m (9M 2022: € 121.9 m).
Adjusted Group EBITDA increased by 13% to € 50.2 m (9M 2022: € 44.6 m); continued work on key collaborations has partially compensated for underutilised capacities as a result of the cyber-attack.

STRENGTHENING ACTIVITIES THROUGH INTEGRATED R&D AND PRECISION MEDICINE PLATFORMS

Multiple new and extended integrated drug discovery and development agreements all along the drug discovery & development value chain (e.g., new INDiGO agreement with Matchpoint Therapeutics)
Extension and expansion of strategic neurodegeneration partnership with Bristol Myers Squibb ("BMS"), and strong progress in strategic targeted protein degradation partnership with BMS
Co-owned pipeline progress: Positive Phase I read-out for EVT8683, start of Phase I trial for EVT401
Further value creation through academic partnerships (BRIDGEs): Launch of "LAB eN²" with Novo Nordisk and academic institutions Harvard University, Mass General Brigham, Yale University, and Beth Israel Deaconess Medical Center
New partnering agreement to strengthen biotech innovators in shared R&D economy with LabCentral, BioLabs, and MBC BioLabs

Events after Period-End

Launch of "65LAB", Evotec’s first BRIDGE partnership in Asia
Co-owned pipeline updates: Presentation of biomarkers data on EVT801, Exscientia decided to de-prioritise EXS21546
New participation in iCARE4CVD, a consortium to personalise prevention and treatment of cardiovascular diseases
New strategic partnership with Dewpoint Therapeutics in oncology

CORPORATE
Opening of new state-of-the-art biology facility on Dorothy Crowfoot Hodgkin Campus

Events after Period-End

Evotec receives SBTi validation and approval of its near-term emission reduction targets
In October, Evotec’s management started the social process of redeploying its chemistry activities out of Marcy (Lyon), as part of its Value Protection Plan ("VPP") 

BUSINESS OUTLOOK FOR FULL-YEAR 2023 AND MID-TERM GOALS 2025 CONFIRMED
Group revenues expected to be in a range of € 750 – 790 m or € 765 – 805 m at constant exchange rates (2022: € 751 m).
Adjusted Group EBITDA expected to be in the range of € 60 – 80 m, translating into € 70 – 90 m at constant exchange rates (2022: € 102 m).
Unpartnered research and development expenses expected to be in a range of € 60 – 70 m (2022: € 70 m).
Mid-term goals target revenue growth to > € 1,000 m, adjusted EBITDA of ≥ € 300 m and unpartnered research and development expenses of > € 100 m.

Due to the criminal cyber-attack discovered on 6 April 2023, productivity was affected in the second and third quarters. In response to the criminal cyber-attack, Evotec took immediate action to contain and remediate the attack by taking its external-facing systems offline. This was deemed necessary to protect all the Company’s partners and stakeholders and meant Evotec could ensure that the integrity of scientific data remained unaffected.

More detailed information and financial tables are available in our interim statement 9M published on the Evotec website under the following link: View Source

WEBCAST / CONFERENCE CALL
The Company is going to hold a conference call to discuss the results as well as provide an update on its performance. The conference call will be held in English.

Webcast details

Date: Wednesday, 08 November 2023

Time: 2.00 pm CET (01.00 pm GMT, 08.00 am EST)

To join the audio webcast and to access the presentation slides, please register via this link.

The on-demand version of the webcast will be available on our website: www.evotec.com/financial-reports.

Conference call details

To join via phone, please pre-register via this link. You will then receive a confirmation email with dedicated dial-in details such as telephone number, access code and PIN to access the call.

A simultaneous slide presentation for participants dialling in via phone is available under this link.