On November 8, 2023 Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, reported that the Company’s senior management team will participate in the following investor conferences in November (Press release, Karyopharm, NOV 8, 2023, View Source [SID1234637262]):

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Jefferies 2023 London Healthcare Conference
Format: Fireside chat
Date: Wednesday, November 15, 2023
Time: 8:00 a.m. ET / 1:00 p.m. GMT

Piper Sandler 35th Annual Healthcare Conference
Format: Fireside chat
Date: Wednesday, November 29, 2023
Time: 4:00 p.m. ET

A live webcast of these events, along with accompanying slides, can be accessed under "Events & Presentations" in the Investor section of the Company’s website, View Source, and will be available for replay for 90 days following each presentation.

On November 8, 2023 Jazz Pharmaceuticals plc (Nasdaq: JAZZ) reported financial results for the third quarter of 2023 and provided business updates (Press release, Jazz Pharmaceuticals, NOV 8, 2023, View Source [SID1234637261]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"We have once again delivered strong financial results from increasingly diversified revenue streams and remain well-positioned for long-term growth. Low-sodium Xywav grew 30% year-over-year despite additional competition, with continued compelling adoption across both narcolepsy and idiopathic hypersomnia (IH). Epidiolex is well-positioned to deliver on its blockbuster potential as a differentiated treatment option with multiple ex-U.S. launches expected through 2024. Oncology net product sales grew 17% year-over-year and our Oncology therapeutic area remains on course to reach approximately $1 billion in annual revenue this year," said Bruce Cozadd, chairman and chief executive officer of Jazz Pharmaceuticals. "We have raised our 2023 total revenue guidance yet again, as well as our Oncology revenue guidance, at the mid-points. We are increasing our investment in R&D based on our confidence in zanidatamab to raise the standard of care for patients and create long-term value for Jazz. Our disciplined capital deployment and strong execution has also enabled us to increase investment in our key commercial franchises, while delivering on our full year GAAP net income and non-GAAP adjusted net income guidance. We remain well-positioned to achieve Vision 2025."

"We now expect as many as five late-stage readouts from our robust R&D pipeline by the end of 2024 and continue to progress multiple early-stage programs in both neuroscience and oncology. We plan to initiate the zanidatamab rolling BLA submission this year for accelerated approval in 2L BTC and expect to complete it in the first half of 2024. Our pivotal, Phase 3 trial of Epidyolex in Japan is progressing well and we now anticipate top-line data in the second half of 2024. Nearer term catalysts include the anticipated readout of JZP150 Phase 2 top-line data in PTSD and initial proof-of-concept from JZP441 in healthy volunteers. The breadth and depth of our expanded R&D pipeline continues to add to the diversification and transformation of our company together with the ability to improve patients’ lives," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development of Jazz Pharmaceuticals.

Key Highlights

•Xywav net product sales grew 30% year-over-year; annualizing at $1.3 billion.
•Total oxybate revenue, including royalties from authorized generics (AGs), is annualizing at $1.9 billion; 68% of 3Q23 total oxybate revenues were driven by Xywav.
•Epidiolex/Epidyolex net product sales grew 9% year-over-year with continued global launch momentum; top-line data from pivotal, Phase 3 trial in Japan expected in 2H24.
•Rylaze net product sales grew 43% year-over-year supported by multiple demand drivers.
•Plan to initiate zanidatamab rolling BLA submission this year for accelerated approval in 2L BTC; expect to complete BLA in 1H24.
•Robust pipeline with as many as five late-stage data readouts expected by the end of 2024.
1

•Increased R&D investment driven by confidence in robust pipeline; reaffirmed full year GAAP net income and non-GAAP adjusted net income (ANI) guidance.

Business Updates

Key Commercial Products
Xywav (calcium, magnesium, potassium, and sodium oxybates) oral solution:
•Xywav net product sales increased 30% to $331.6 million in 3Q23 compared to the same period in 2022; expect Xywav to remain the oxybate of choice.
•There were approximately 12,050 active Xywav patients exiting 3Q23.
•The Company continued to present data supporting its scientific leadership in sleep disorders and highlighting the impact of low-sodium Xywav for patients with narcolepsy and IH.
◦At Psych Congress 2023, a review of multiple clinical trials demonstrated oxybate improves sleep quality, sleep architecture and measures of disrupted nighttime sleep in narcolepsy, independent of once- or twice-nightly dosing.
◦At World Sleep 2023, results from the TENOR study of adults with narcolepsy showed the most common patient-reported reasons for utilizing Xywav individualized dosing regimens were to avoid morning grogginess, help fall asleep and improve sleep quality. Results from another study, CV-RHYTHM, found patients with IH experienced a greater burden of cardiovascular comorbidities, including stroke, heart attacks and heart failure than those without IH, emphasizing the importance of holistic management to treat under-recognized sleep disorders.

Xywav for Narcolepsy:
•Continued growth of Xywav in narcolepsy, despite additional competition, with approximately 9,500 narcolepsy patients taking Xywav exiting 3Q23.
•The benefits of reducing sodium intake continue to resonate with patients and prescribers.

Xywav for Idiopathic Hypersomnia (IH):
•There were approximately 2,550 IH patients taking Xywav exiting 3Q23.
•Jazz survey of sleep specialists indicates 70% anticipate increasing their prescribing of Xywav for IH over the next six months, and new prescribers continued to grow in 3Q23.
•Xywav remains the first and only FDA-approved treatment demonstrating improvement across multiple symptoms, including sleep inertia, which has a significant impact on patients’ quality of life and daily function.

Xyrem (sodium oxybate) oral solution:
•Xyrem net product sales decreased 51% to $125.1 million in 3Q23 compared to the same period in 2022, reflecting the continued adoption of Xywav by patients with narcolepsy and the launch of high-sodium oxybate AGs in 2023.

Oxybate (Xywav, Xyrem and AG Royalties):
•Total oxybate revenue, including royalties from AGs, is annualizing at $1.9 billion.
•Royalties from high-sodium oxybate AGs were $28.9 million in 3Q23, which reflect a significant increase over 1H23 and the fixed-rate royalty structures of the AG agreements in 2H23.

Epidiolex/Epidyolex (cannabidiol):
•Epidiolex/Epidyolex net product sales increased 9% to $213.7 million in 3Q23 compared to the same period in 2022.
•Epidiolex/Epidyolex global prescriber base increasing with multiple launches ongoing and anticipated outside of the U.S. through 2024, further positioning Epidiolex/Epidyolex to achieve blockbuster status.
2

•Demand driven by compelling efficacy data from Epidiolex in combination with clobazam, increased penetration in adults and long-term care settings, and beyond seizure benefits from the BECOME caregiver survey in in Dravet syndrome (DS) and Lennox-Gastaut syndrome (LGS).
•Additional opportunity for growth coming from continued data generation, including potential beyond seizure benefits from the EpiCom study in tuberous sclerosis complex (TSC) and multiple publications at AES 2023.
•A pivotal, Phase 3 trial of Epidyolex in DS, LGS and TSC in Japan is enrolling patients and top-line data from the trial are expected in 2H24.

Rylaze/Enrylaze (asparaginase erwinia chrysanthemi (recombinant)-rywn):
•Rylaze net product sales increased 43% to $104.9 million compared to the same period in 2022.
•Continued strong Rylaze demand driven by multiple factors, including increased use in adolescents and young adults with acute lymphoblastic leukemia (ALL) and additional switching of patients from E. coli-based asparaginase to Rylaze due to non-hypersensitivity treatment-related issues.
•The European Commission granted marketing authorization for Enrylaze (JZP458; a recombinant Erwinia asparaginase or crisantaspase), marketed as Rylaze in the U.S. and Canada, for use as a component of a multi-agent chemotherapeutic regimen for the treatment of ALL and lymphoblastic lymphoma in adult and pediatric patients (1 month and older) who developed hypersensitivity or silent inactivation to E. coli-derived asparaginase. The Company is planning to begin a rolling launch later this year.

Zepzelca (lurbinectedin):
•Zepzelca net product sales increased 11% to $78.0 million in 3Q23 compared to the same period in 2022.
•The Company expects top-line data from the Phase 3 trial evaluating first-line (1L) use of Zepzelca to readout at the end of 2024 or early 2025. The trial is assessing the combination with Tecentriq (atezolizumab), compared to Tecentriq alone, as maintenance therapy in patients with extensive-stage small cell lung cancer after induction chemotherapy, in partnership with F. Hoffmann-La Roche Ltd (Roche).

Key Pipeline Highlights
Zanidatamab:
•Zanidatamab is a novel bispecific antibody that simultaneously binds two non-overlapping epitopes of HER2, resulting in multiple mechanisms of action, potent immune activation and encouraging antitumor activity in patients.
•The Company plans to initiate the zanidatamab rolling BLA submission this year for accelerated approval in 2L BTC and expects to complete the rolling submission 1H24.
•The Company has alignment with FDA on a confirmatory trial in 1L metastatic BTC, where there remains unmet patient need.
•The pivotal HERIZON-GEA-01 trial, evaluating zanidatamab in 1L gastroesophageal adenocarcinoma, is ongoing and top-line data are expected in 2024.
•The Company, along with partners, presented zanidatamab data at ESMO (Free ESMO Whitepaper) Congress 2023. Results from a Phase 1b/2 study of zanidatamab plus chemotherapy in combination with tislelizumab for the 1L treatment of HER2-positive gastric/gastroesophageal junction adenocarcinoma demonstrated antitumor activity with a confirmed ORR of 75.8%, median duration of response of 22.8 months and median PFS of 16.7 months and safety was consistent with previous findings.

JZP150:
•JZP150, a selective fatty acid amide hydrolase, or FAAH, inhibitor, is in clinical development for the potential treatment of post-traumatic stress disorder (PTSD).
3

•Patient enrollment is now complete in the Phase 2 PTSD trial and top-line data are expected in January 2024.
•The Company received Fast Track Designation for JZP150 development in PTSD from FDA, underscoring the significant unmet medical needs of patients.

Suvecaltamide (JZP385):
•Suvecaltamide, a highly selective and state dependent modulator of T-type calcium channels, is in clinical development for the treatment of essential tremor (ET) and Parkinson’s disease tremor.
•Patient enrollment is ongoing in the Phase 2b ET trial and top-line data readout is anticipated in 1H24. A Phase 2 trial in patients with Parkinson’s disease tremor is ongoing.

JZP441:
•JZP441 is a potent, highly selective oral orexin-2 receptor agonist designed to activate orexin signaling with the potential to be applicable in the treatment of narcolepsy, IH and other sleep disorders.
•A Phase 1 development program to evaluate safety, tolerability, pharmacokinetics and pharmacodynamics of JZP441 in sleep-deprived healthy volunteers is ongoing.
•The Company expects initial proof of concept in healthy volunteers in 2023.

JZP815:
•JZP815 potently inhibits both monomer- and dimer-driven RAF signaling and prevents paradoxical pathway activation induced by BRAF selective inhibition.
•A Phase 1 trial evaluating JZP815 in patients with advanced or metastatic solid tumors with MAPK pathway alterations is ongoing and a trial in progress poster of the Phase 1 study was presented at ESMO (Free ESMO Whitepaper) Congress 2023.

JZP898:
•JZP898 is an engineered IFNα cytokine pro-drug that is activated specifically within the tumor microenvironment where it can stimulate IFNα receptors on cancer-fighting immune effector cells.
•JZP898 received Investigational New Drug application clearance and the Company expects to initiate a Phase 1 clinical trial by the end of the year.

Continued Repurchases under Previously Announced $1.5 Billion Share Repurchase Program

The Company continued repurchases of its ordinary shares on the open market in the third quarter of 2023 as part of its previously authorized and announced share repurchase program. As of September 30, 2023, approximately $261 million remained available and authorized for share repurchases, after the purchase of approximately $75 million shares during the third quarter of 2023. The timing and amount of repurchases under the program will depend on a variety of factors, including the price of the Company’s ordinary shares, alternative investment opportunities, restrictions under the Company’s credit agreement, corporate and regulatory requirements and market conditions.

Financial Highlights
Three Months Ended
September 30, Nine Months Ended
September 30,
(In thousands, except per share amounts) 2023 2022 2023 2022
Total revenues $ 972,140 $ 940,652 $ 2,822,269 $ 2,687,251
GAAP net income (loss) $ 146,820 $ (19,648) $ 320,678 $ 16,664
Non-GAAP adjusted net income $ 340,148 $ 370,438 $ 950,538 $ 937,837
GAAP earnings (loss) per share $ 2.14 $ (0.31) $ 4.67 $ 0.26
Non-GAAP adjusted EPS $ 4.84 $ 5.17 $ 13.29 $ 13.21

GAAP net income (loss) for 3Q23 was $146.8 million, or $2.14 per diluted share, compared to $(19.6) million, or $(0.31) per diluted share, for 3Q22.
Non-GAAP adjusted net income for 3Q23 was $340.1 million, or $4.84 per diluted share, compared to $370.4 million, or $5.17 per diluted share, for 3Q22.
Reconciliations of applicable GAAP reported to non-GAAP adjusted information are included at the end of this press release.

Total Revenues
Three Months Ended
September 30, Nine Months Ended
September 30,
(In thousands) 2023 2022 2023 2022
Xywav $ 331,633 $ 255,936 $ 935,958 $ 677,041
Xyrem 125,110 256,039 463,009 772,957
Epidiolex/Epidyolex 213,711 196,218 604,846 529,400
Sativex 4,627 3,220 14,531 12,104
Sunosi1
— — — 28,844
Total Neuroscience 675,081 711,413 2,018,344 2,020,346
Rylaze 104,859 73,513 292,479 200,687
Zepzelca 77,994 70,320 215,523 197,943
Defitelio/defibrotide 47,730 49,452 132,917 153,637
Vyxeos 29,827 30,067 100,583 97,714
Total Oncology 260,410 223,352 741,502 649,981
Other 2,907 1,001 9,758 3,576
Product sales, net 938,398 935,766 2,769,604 2,673,903
High-sodium oxybate AG royalty revenue 28,921 — 36,531 —
Other royalty and contract revenues 4,821 4,886 16,134 13,348
Total revenues $ 972,140 $ 940,652 $ 2,822,269 $ 2,687,251

Total revenues increased 3% in 3Q23 compared to the same period in 2022.
•Total neuroscience revenue, including high-sodium oxybate AG royalty revenue, was $704.0 million in 3Q23 compared to $711.4 million in 3Q22. Neuroscience net product sales in 3Q23 decreased 5% to $675.1 million compared to the same period in 2022 driven by decreased Xyrem revenues, reflecting the continued strong adoption of Xywav by patients with narcolepsy and availability of high-sodium oxybate AGs, offset by increased Xywav and Epidiolex/Epidyolex net product sales. High-sodium oxybate AG royalty revenue relates primarily to royalty revenue received from Hikma Pharmaceuticals plc on net sales of a high-sodium oxybate AG product.

•Oncology net product sales in 3Q23 increased 17% to $260.4 million compared to the same period in 2022 primarily driven by the continued growth in Rylaze product sales, which increased 43% to $104.9 million.

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

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]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"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.