On November 9, 2021 Brickell Biotech, Inc. ("Brickell" or the "Company") (Nasdaq: BBI), a clinical-stage pharmaceutical company striving to transform patient lives by developing innovative and differentiated prescription therapeutics for the treatment of dermatologic, autoimmune, and other debilitating diseases, reported financial results for the third quarter ended September 30, 2021 and provided a corporate update (Press release, Vical, NOV 9, 2021, View Source [SID1234595211]).

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"This has been an exciting period for Brickell, as we announced positive data from our Phase 3 pivotal clinical studies of sofpironium bromide gel, 15% and expanded our pipeline with the acquisition of a Phase 1-ready DYRK1A inhibitor and cutting-edge platform with broad potential in autoimmune and inflammatory disorders. We look to build on this momentum by focusing on several near-term clinical, regulatory, and operational milestones that we believe can drive our growth," commented Robert Brown, Chief Executive Officer of Brickell. "We were pleased to announce last month that the Phase 3 Cardigan I and Cardigan II studies of sofpironium bromide gel, 15% in patients with primary axillary hyperhidrosis, or excessive underarm sweating, achieved statistical significance on all primary and secondary efficacy endpoints. Based on the positive results from these studies, we expect to submit an NDA for sofpironium bromide gel, 15% to the FDA in mid-2022. As we plan the commercial strategy for sofpironium bromide gel, 15%, if approved, we are evaluating all available options to maximize commercial product success and long-term value for the company."
"We look forward to advancing the development of our DYRK1A inhibitor programs that aim to restore immune balance with a novel and differentiated small molecule approach, which we believe will help improve the lives of patients with autoimmune diseases. To this end, we expect to advance our lead DYRK1A inhibitor program, BBI-02, into a Phase 1 clinical study in the first half of 2022, with topline results anticipated by the end of 2022. We look forward to providing updates on this planned study in the coming months," continued Mr. Brown.
Business and Recent Developments
•Reported positive topline results from two U.S. Phase 3 pivotal clinical studies of sofpironium bromide gel, 15%, each of which enrolled approximately 350 patients who were nine years of age and older with primary axillary hyperhidrosis. Both studies achieved statistical significance on all primary and secondary efficacy endpoints, and data demonstrated that sofpironium bromide gel, 15% was generally well-tolerated.
•Acquired exclusive, worldwide rights to research, develop, and commercialize novel therapeutics generated from a proprietary DYRK1A inhibitor platform with broad potential in autoimmune and inflammatory diseases. The acquisition includes BBI-02, a Phase 1-ready, highly selective, and orally bioavailable DYRK1A inhibitor; BBI-03, a topically applied preclinical DYRK1A inhibitor; and a platform of DYRK1A inhibitors with potential to create next-generation kinase inhibitors targeting neuroinflammatory and autoimmune disorders.
•Hosted a Key Opinion Leader ("KOL") webinar featuring a presentation by KOL Bernard Khor, M.D., Ph.D., Benaroya Research Institute at Virginia Mason, who discussed the latest findings on the novel target DYRK1A, its role in autoimmune and inflammatory diseases, and the broad therapeutic potential of restoring immune homeostasis by inhibiting DYRK1A. A replay of the event can be found on the Events and Presentations section of the Company’s website at View Source

•Expanded leadership team by appointing Dr. Monica Luchi as Chief Medical Officer to oversee the Company’s clinical development strategy, including for the DYRK1A inhibitor pipeline, and medical affairs functions.
•Brickell’s development partner, Kaken Pharmaceutical Co., Ltd. ("Kaken"), continued conduct of a Phase 1 clinical study in Japan assessing the pharmacokinetics (PK), safety, and efficacy of sofpironium bromide gel in patients with primary palmoplantar hyperhidrosis.
•Strengthened cash balance with net proceeds of $8.9 million received from a public offering of the Company’s common stock in October 2021.
Upcoming Milestones
•Prospective NDA submission to the U.S. FDA for sofpironium gel, 15% in mid-2022.
•Intend to progress BBI-02 into a Phase 1 clinical study in Canada in the first half of 2022, with topline results expected by the end of 2022.
•Expect to conduct formulation development activities for BBI-03 throughout 2022, and to select and initiate development of a lead next-generation candidate from the DYRK1A inhibitor platform with potential for the treatment of neuroinflammatory and/or autoimmune diseases.
Third Quarter 2021 Financial Results
The Company reported cash and cash equivalents of $21.4 million as of September 30, 2021, compared to $30.1 million as of December 31, 2020.
Revenue was $0.1 million for the third quarter of 2021, which consisted of royalty revenue recognized related to sales of ECCLOCK in Japan by Kaken. Revenue was $0.1 million for the third quarter of 2020, which was driven by collaboration revenue recognized for research and development funding provided by Kaken to Brickell in 2018.
Research and development expenses were $10.2 million for the third quarter of 2021, compared to $1.3 million for the third quarter of 2020. This increase was primarily due to a $4.8 million expense recorded related to the upfront payment in cash and shares of our common stock to Voronoi Inc. in exchange for exclusive, worldwide rights to the proprietary DYRK1A inhibitor platform and an increase of $3.8 million in clinical costs related to sofpironium bromide.
General and administrative expenses were $3.3 million for the third quarter of 2021, compared to $3.2 million for the third quarter of 2020, remaining generally consistent with the comparable period.
Brickell’s net loss was $13.3 million for the third quarter of 2021 compared to $4.3 million for the third quarter of 2020.
Conference Call and Webcast Information
Brickell’s management will host a conference call today at 4:30 p.m. ET to discuss the financial results and recent corporate developments. The dial-in number for the conference call is 1-877-705-6003 for domestic participants and 1-201-493-6725 for international participants, with Conference ID #13723603. A live webcast of the conference call can be accessed at View Source or through the Brickell Biotech website at View Source A replay will be available on this website shortly after conclusion of the event for approximately 90 days.
About Sofpironium Bromide
Sofpironium bromide is a new chemical entity that belongs to a class of medications called anticholinergics. Anticholinergics block the action of acetylcholine, a chemical that transmits signals within the nervous system that are responsible for a range of bodily functions, including activation of the sweat glands. Sofpironium bromide was retrometabolically designed. Retrometabolic drugs are designed to exert their action locally and are potentially rapidly metabolized into a less active form once absorbed into the blood. Brickell has developed sofpironium bromide gel, 15% as a potential best-in-class, self-administered, once daily, topical therapy for the treatment of primary axillary hyperhidrosis, also known as excessive underarm sweating. Sofpironium bromide gel, 15% has completed a U.S. Phase 3 pivotal clinical program for the treatment of primary axillary hyperhidrosis, which achieved statistical significance on all primary and secondary efficacy endpoints, and sofpironium bromide gel, 15% was generally well-tolerated. Sofpironium bromide gel, 5% is approved in Japan for the same indication

under the brand name ECCLOCK. Sofpironium bromide was discovered at Bodor Laboratories, Inc. by Dr. Nicholas Bodor D.Sc., d.h.c. (multi), HoF, Graduate Research Professor Emeritus, University of Florida.
About the DYRK1A Inhibitor Platform
In August 2021, Brickell acquired exclusive, worldwide rights to research, develop, and commercialize novel therapeutics generated from a proprietary DYRK1A inhibitor platform. These novel DYRK1A inhibitors aim to restore immune balance in patients whose immune system has become dysregulated. Based on the promising preclinical efficacy data generated to date on these novel DYRK1A inhibitor programs, Brickell believes this platform has the potential to offer first-in-class, new and potent therapies across a wide array of autoimmune and inflammatory diseases. The initial lead program that the Company expects to advance is BBI-02, a Phase 1-ready, highly selective, and orally bioavailable DYRK1A inhibitor that has demonstrated promising results in various preclinical models, including atopic dermatitis and rheumatoid arthritis. Preclinical data have shown BBI-02 to drive regulatory T-cell differentiation while dampening pro-inflammatory TH17 cells and MyD88/IRAK4-related signaling pathways. Unlike many existing therapies, as well as those currently being investigated, BBI-02 may have the ability to target both the adaptive and innate immune imbalance simultaneously, potentially resulting in, or substantially achieving, restoration of immune homeostasis that, if proven, would represent a paradigm shift in the treatment of certain autoimmune and inflammatory diseases. The platform also includes BBI-03, a topically applied preclinical DYRK1A inhibitor, and has the potential to create next generation kinase inhibitors (NCEs) targeting neuroinflammatory and autoimmune disorders.

On November 9, 2021 Delcath Systems, Inc. (Nasdaq: DCTH), an interventional oncology company focused on the treatment of rare primary and metastatic cancers of the liver, reported business highlights and financial results for the third quarter ended September 30, 2021 (Press release, Delcath Systems, NOV 9, 2021, View Source [SID1234595228]).

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Recent Business Highlights

During and since the third quarter Delcath:

Entered a debt facility with Avenue Venture Opportunities Fund, L.P. providing up to $20 million with an initial $15 million funded at closing,
Submitted to and received approval from the FDA for an expanded access protocol for the use of HEPZATO Kit (melphalan hydrochloride for injection/hepatic delivery system) in the treatment of patients with liver dominant metastatic ocular melanoma,
Updated guidance of the Class 2 resubmission of the NDA to mid-year from the end of the first quarter,
Hired 3 senior executives in clinical operations, regulatory and medical affairs to support the resubmission of the NDA and further clinical development of HEPZATO, and
Announced it will host a comprehensive Investor Update event on Thursday, December 2nd, from 10:00am ET – 1:00pm ET covering FOCUS trial results as well as development plans for the use of HEPZATO in the treatment of patients with intrahepatic cholangiocarcinoma and colorectal cancer.
In addition, during the third quarter independent investigators:

Presented three abstracts on the use of Chemosat Hepatic Delivery System with Melphalan in the treatment of metastatic ocular melanoma (mOM) at the 2021 Cardiovascular and Interventional Radiological Society of Europe conference (CIRSE) including,
Safety and toxicity of combining hepatic percutaneous perfusion with ipilimumab plus nivolumab in advanced uveal melanoma: phase 1b of the CHOPIN Trial1
Long-term results of percutaneous hepatic perfusion with melphalan in patients with unresectable liver metastases from uveal melanoma: a multicenter retrospective study2
Safety and efficacy of chemosaturation with percutaneous hepatic perfusion of melphalan for metastatic uveal melanoma: an 8-year retrospective study of 250 interventions in 81 patients3
Published Repeated percutaneous hepatic perfusion with melphalan can maintain long-term response in patients with liver cancers4 in the journal Cardiovascular and Interventional Radiology.
"It’s very exciting to see the initial results of the CHOPIN Trial. These early results in the first trial to combine percutaneous hepatic perfusion with combination immunotherapy show promise with no dose limiting toxicities observed to date. The significant disease control and repeatability of the procedure with limited cumulative toxicity observed in these recent publications is consistent with what we have seen documented from other institutions," said Dr. Johnny John, SVP Clinical Operations and Medical Affairs.

"During the quarter we strengthened our balance sheet and added senior personnel to the Delcath team," said Gerard Michel, CEO of Delcath. "With the additional capital and senior leadership, Delcath has the required resources to accomplish its strategic priorities – the filing of the HEPZATO NDA in mid-2022, preparing for the subsequent US launch when approved, and expanding the development of HEPZATO into additional areas of high unmet need."

Financial Results:

Income Statement Highlights.

Product revenue for the three months ended September 30, 2021 was approximately $522 thousand, compared to $466 thousand for the prior year period from our sales of CHEMOSAT procedures in Europe. Selling, general and administrative expenses were approximately $4.0 million compared to $2.0 million in the prior year quarter. Research and development expenses for the quarter were $3.0 million compared to $3.3 million in the prior year quarter. Total operating expenses for the quarter were $7.0 million compared with $5.3 million in the prior year quarter. Expenses for the quarter included approximately $2.5 million of stock option expense compared to no stock option expense in the prior year quarter.

The Company recorded a net loss for the three months ended September 30, 2021, of $7.1 million, compared to a net loss of $5.0 million for the same period in 2020.

Balance Sheet Highlights.

On September 30, 2021, we had cash, cash equivalents and restricted cash totaling $29 million, as compared to cash, cash equivalents and restricted cash totaling $11.1 million at September 30, 2020. During the three months ended September 30, 2021 and September 30, 2020, we used $16.2 million and $17.8 million, respectively, of cash in our operating activities.

On August 6, 2021 we closed a $20 million venture debt financing transaction with Avenue Venture Opportunities Fund, L.P. ("Avenue Venture Fund"), at which time an initial $15 million tranche of the loan was funded, including $4 million funded into a restricted account to be released upon achievement of certain milestones. The Company may request an additional $5 million tranche of the loan between October 1, 2022 and December 31, 2022, the funding of which will be at Avenue Venture Fund’s discretion.

Also, on August 6, 2021, we amended two existing convertible notes through an extension of the term of the notes until 2024 and lowered the conversion factor in consideration for the notes becoming subordinate to the Avenue Venture Fund debt.

Additional details concerning the Avenue Venture Fund facility and modification of the existing convertible notes are contained in the Company’s Current Report on Form 8-K filed with the Securities and Exchange Commission on August 11, 2021.

Conference Call Information

To participate in this event, dial approximately 5 to 10 minutes before the beginning of the call.

On November 9, 2021 Ziopharm Oncology, Inc. ("Ziopharm" or the "Company") (Nasdaq: ZIOP), reported the presentation of preclinical data highlighting the potential of neoantigen-specific TCR-T cells for the treatment of solid tumors at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 2021 Annual Meeting (Press release, Ziopharm, NOV 9, 2021, View Source [SID1234594831]).

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"We are pleased to share preclinical data demonstrating the versatility of our Sleeping Beauty technology to develop neoantigen-specific TCR-T cells with the potential to address a wide range of solid tumor indications," commented Raffaele Baffa, M.D., Ph.D., Chief Medical Officer & EVP, Research & Development. "Our TCR-T library approach allows us to develop safe, effective and durable therapies for any patient with a matching neoantigen/HLA combination within our library. We are working diligently to initiate our Phase 1/2 TCR-T Library trial in the first half of 2022 as well as continue to expand our library of TCRs in order to increase the pool of eligible patients who could benefit from these therapies."

Details of Ziopharm’s SITC (Free SITC Whitepaper) 2021 presentation are as follows:

Title: Neoantigen-specific TCR-T cells targeting shared hotspot mutations for adoptive cell therapy in common epithelial cancers
Presenter: Drew Deniger, Ph.D., Ziopharm Oncology
Date/Time: Saturday, Nov. 13, 2021 from 7:00 a.m. – 8:30 p.m. ET
Location: Walter E. Washington Convention Center, Hall E
Abstract Number: 226

In the study presented at SITC (Free SITC Whitepaper), Ziopharm’s non-viral gene transfer technology, Sleeping Beauty, was used to develop TCR-T cells targeting EGFR, KRAS and p53 neoantigens, which are present in cancer cells but not in normal tissue, and are presented by a variety of human leukocyte antigen (HLA) molecules on the cancer cell surface. Ziopharm’s Sleeping Beauty technology exhibited greater than 60% expression of the introduced neoantigen-specific TCRs in the generated TCR-T cells. The study demonstrated that the neoantigen-specific TCR-T cells successfully targeted tumor cells expressing EGFR, KRAS and p53 neoantigens in conjunction with the matching HLA restriction. Importantly, these TCR’s did not recognize cells lacking the matching mutations and HLA restrictions.

On November 9, 2021 Eagle Pharmaceuticals, Inc. (Nasdaq: EGRX) ("Eagle" or the "Company") reported financial results for the three and nine months ended September 30, 2021 (Press release, Eagle Pharmaceuticals, NOV 9, 2021, View Source [SID1234594847]).

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Business and Recent Highlights:

Entered into a worldwide licensing agreement for the commercial rights to CAL02, a novel first-in-class antitoxin agent ready for Phase 2b/3 development for the treatment of severe bacterial pneumonia in combination with traditional antibacterial drugs.
Vasopressin updates:
In August 2021, received favorable decision from the U.S. District Court for the District of Delaware that Eagle’s proposed vasopressin product does not infringe any of the patents Par Pharmaceutical, Inc. asserted against Eagle.
U.S. Food and Drug Administration ("FDA") maintained Priority Review for the Company’s ANDA with December 15, 2021 GDUFA date.
Received a 30-day information request from the FDA; Eagle fully responded to the request on September 20, 2021, and there are no other review requests outstanding.
Granted U.S. Patent No. 11,103,483, "Formulations of Bendamustine," which has been listed in the FDA Orange Book for BENDEKA and BELRAPZO.
Entered into a licensing agreement for the U.S. commercial rights to landiolol, a leading hospital emergency use product in Europe and Japan. Landiolol is currently approved in Europe for the treatment of non-compensatory sinus tachycardia and tachycardic supraventricular arrhythmias. Eagle will support the submission of a new drug application to the FDA seeking approval for landiolol for the short-term reduction of ventricular rate in patients with supraventricular tachycardia, including atrial fibrillation and atrial flutter.
Financial Highlights

Third Quarter 2021

Total revenue for Q3 2021 was $39.9 million, compared to $49.9 million in Q3 2020, primarily reflecting lower product sales of BELRAPZO and BENDEKA, partially offset by higher product sales of TREAKISYM.
Q3 2021 net loss was $5.6 million, or $0.43 per basic and diluted share, compared to net income of $7.1 million, or $0.52 per basic and $0.51 diluted share in Q3 2020.
Q3 2021 adjusted non-GAAP net income was $7.5 million, or $0.57 per basic and $0.56 per diluted share, compared to adjusted non-GAAP net income of $16.1 million, or $1.19 per basic and $1.17 per diluted share, in Q3 2020.
Cash and cash equivalents were $99.7 million, net accounts receivable was $45.3 million, and debt was $28.0 million as of September 30, 2021.
"We are preparing for two significant product launches, vasopressin and PEMFEXY, expected within the next ninety days that we believe will meaningfully increase the revenue and profitability of Eagle. With the recent licensing of CAL02 and landiolol, our expectation going forward is that we will utilize our cash and possibly the balance sheet to further strengthen the pipeline and portfolio," stated Scott Tarriff, President and Chief Executive Officer of Eagle Pharmaceuticals.

Third Quarter 2021 Financial Results

Total revenue for the three months ended September 30, 2021 was $39.9 million, as compared to $49.9 million for the three months ended September 30, 2020.

Q3 2021 BELRAPZO product sales were $4.9 million, compared to $8.7 million in Q3 2020.

Q3 2021 RYANODEX product sales were $4.5 million, compared to $4.2 million in Q3 2020.

Royalty revenue was $27.7 million in the third quarter of 2021, compared to $27.6 million in the third quarter of 2020. BENDEKA royalties were $26.5 million in the third quarter of 2021, compared to $27.6 million in the third quarter of 2020. A summary of total revenue is outlined below:

Gross Margin was 79% during the third quarter of 2021, as compared to 76% in the third quarter of 2020. The increase in gross margin for the third quarter of 2021 was driven by revenue mix.

R&D expense was $23.3 million for the third quarter of 2021, compared to $4.8 million in the third quarter of 2020. The increase includes a $10.0 million upfront payment related to our license agreement with Combioxin for CAL02, a $5.0 million upfront expense related to our licensing agreement with AOP Orphan for landiolol, a $0.8 million increase in development and pre-launch inventory costs for vasopressin and a $1.1 million increase related to PEMFEXY. Excluding stock-based compensation and other non-cash and non-recurring items, R&D expense during the third quarter of 2021 was $7.6 million.

SG&A expenses in the third quarter of 2021 totaled $18.5 million compared to $17.7 million in the third quarter of 2020. This increase is primarily related to higher external legal costs partially offset by a decrease in stock-based compensation expense. Excluding stock-based compensation and other non-cash and non-recurring items, third quarter 2021 SG&A expense was $14.5 million.

Net loss for the third quarter of 2021 was $5.6 million, or $0.43 per basic and diluted share, compared to net income of $7.1 million, or $0.52 per basic and $0.51 per diluted share, in the third quarter of 2020, due to the factors discussed above.

Adjusted non-GAAP net income for the third quarter of 2021 was $7.5 million, or $0.57 per basic and $0.56 per diluted share, compared to adjusted non-GAAP net income of $16.1 million or $1.19 per basic and $1.17 per diluted share in the third quarter of 2020. For a full reconciliation of adjusted non-GAAP net income to the most comparable GAAP financial measures, please see the tables at the end of this press release.

2021 Expense Guidance

R&D spend in 2021, on a non-GAAP basis, is expected to be $34-$38 million, as compared to $27.8 million in 2020.
SG&A spend in 2021, on a non-GAAP basis, is expected to be $52-$56 million, as compared to $50.9 million in 2020.
The guidance provided in this section represents forward-looking information, and actual results may vary. Please see the risks and assumptions referred to in the Forward-Looking Statements section of this press release.
Liquidity

As of September 30, 2021, the Company had $99.7 million in cash and cash equivalents plus $45.3 million in net accounts receivable. The Company had $28.0 million in outstanding debt. Therefore, as of September 30, 2021, the Company had net cash plus receivables of $117.0 million.

In the third quarter of 2021, the Company purchased $8.3 million of its common stock as part of its $160.0 million Share Repurchase Program. From August 2016 through September 30, 2021, the Company has repurchased $219.4 million of its common stock.

Conference Call

As previously announced, Eagle management will host its third quarter 2021 conference call as follows:

A replay of the conference call will be available for one week after the call’s completion by dialing 800-839-8292 (US) or 402-220-6069 (International) and entering conference call ID EGRXQ321. The webcast will be archived for 30 days at the aforementioned URL.

On November 9, 2021 Immatics N.V. (NASDAQ: IMTX, "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell-redirecting cancer immunotherapies, reported an interim clinical data update from its TCR-engineered cell therapy (TCR-T) approach ACTengine IMA203 targeting PRAME (Press release, Immatics, NOV 9, 2021, View Source [SID1234594863]). Data from patients treated at the first three of four dose levels of the ongoing IMA203 Phase 1a dose escalation study show a high preliminary objective response rate (partial responses according to RECIST 1.1) at doses below 1 billion total transduced cells. The data will be presented as a late-breaking oral presentation on Saturday, November 13 at 12:00-12:15 pm EST at the 36th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper). In addition, Immatics will present preclinical proof-of-concept data for its next-generation IMA203CD8 candidate at the SITC (Free SITC Whitepaper) Annual Meeting on Friday, November 12 and will provide an overall update on all IMA200 programs including IMA201 (MAGEA4/A8) and IMA202 (MAGEA1) in a conference call on November 9, 2021 at 8:30 am EST.

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Key clinical findings from IMA203 Phase 1a trial
In the ongoing ACTengine IMA203 trial, Immatics is treating advanced solid cancer patients utilizing TCR-T cells directed against an HLA-A*02-presented peptide derived from preferentially expressed antigen in melanoma (PRAME). PRAME is homogenously expressed and highly prevalent across several solid cancer indications. The chosen PRAME target peptide has been identified by Immatics’ proprietary mass spectrometry-based target discovery platform XPRESIDENT, demonstrating natural and specific occurrence of the target on tumors at high copy numbers.

Clinical and biological activity: IMA203 demonstrates objective responses (RECIST 1.1.) at low cellular doses across several solid cancer types

At data cut-off on October 5, 2021, 18 patients received ACTengine IMA203 T cells across dose level 1 (DL1) to dose level 4 (DL4).
All patients were heavily pretreated with a median of 4 lines of prior systemic treatment.
16 patients were evaluable for tumor response analysis according to RECIST 1.1 with at least one post-treatment tumor assessment at the time of data cut-off. All 16 patients received dose levels 1 to 3 – below 1 billion total transduced cells. For the remaining 2 patients, the first tumor response assessment is still pending.
15 out of 16 patients (94%) achieved disease control. Tumor shrinkage was observed in 14 patients (88%).
8 out of 16 patients (50%) showed objective responses; onset of responses in all cases was detected within 6 weeks following infusion of IMA203 T cells.
All responses occurred above DL1; 8 out of 13 patients (62%) treated at DL20F1 and DL3 receiving up to 0.59 billion total transduced cells had objective partial responses. Responses were observed in patients with synovial sarcoma, malignant melanoma, uveal melanoma, and head and neck cancer.
As of data cut-off, partial responses were confirmed in subsequent scans in two synovial sarcoma patients and one uveal melanoma patient.
Longer follow-up is required for patients infused at higher dose levels DL3 and DL4 are required to assess response durability and response rate at target dose.
IMA203 continues to show high levels of T cell engraftment, persistence, and tumor infiltration at first three dose levels. Clinical response was associated (p=0.016) with infiltration of IMA203 T cells into the tumor tissue and showed an emerging trend towards higher peak vector copies of IMA203 T cells in blood (p=0.065) – supporting the mechanism-of-action.
The ACTengine IMA203 trial is currently recruiting patients to the 4th and highest dose level (up to approximately 2.5 billion total transduced cells) of the Phase 1a dose escalation cohort.
Preliminary Objective Response Rates (ORR; RECIST 1.1, confirmed and unconfirmed)

Dose Level ORR
DL1 0/3 (0%)
DL21 6/10 (60%)
DL3 2/3 (67%)

All dose levels DL21 & DL3
All comers 8/16 (50%) 8/13 (62%)
Melanoma 3/3 (100%) 3/3 (100%)
Head & Neck Cancer 1/3 (33%) 1/1 (100%)
Synovial Sarcoma 3/5 (60%) 3/5 (60%)
Uveal Melanoma 1/2 (50%) 1/2 (50%)
Safety: IMA203 treatment was well tolerated with transient and manageable treatment-emergent adverse events (TEAEs)

At data cut-off on October 5, 2021, 19 patients were evaluable for safety analysis.
Most frequent TEAEs included expected transient cytopenia (Grade 1-4) associated with lymphodepletion and transient low to moderate (Grade 1-2) cytokine release syndrome (CRS) or immune effector cell associated neurotoxicity syndrome (ICANS).
No additional dose limiting toxicities (DLT) were observed since the previous data release on March 17, 2021.

"We observed multiple clinical responses early-on during dose escalation and saw anti-tumor activity at much lower doses than would have been expected in the field of TCR-T. IMA203 T cells will now be tested at the target dose level and have the potential to provide meaningful benefits to patients with advanced stages of cancer," commented Martin Wermke, MD, Coordinating Investigator of Immatics’ ACTengine trials in Germany and Head of the Early Clinical Trial Unit of the National Center for Tumor Diseases at the University Hospital Carl Gustav Carus in Dresden, Germany. "I am looking forward to presenting this exciting data set to the scientific and medical community at SITC (Free SITC Whitepaper) and to supporting the further development of IMA203."

Following the completion of the dose escalation portion of the study (Phase 1a) and the determination of the recommended Phase 2 dose (RP2D), Immatics plans to expand the IMA203 study to multiple Phase 1b (dose expansion) study cohorts:

IMA203 as a monotherapy
IMA203 in combination with an immune checkpoint inhibitor
IMA203CD8, next-generation TCR-T where IMA203 cells are co-transduced with a CD8 co-receptor

Cedrik Britten, M.D., Chief Medical Officer at Immatics, commented: "The unexpected high clinical response rate in PRAME-positive patients before reaching our target cell dose has shifted our expectations of what cell therapy could potentially achieve in solid cancers. This is a very promising first step, which encourages us to double down efforts for a focused development strategy of our programs targeting PRAME. Our immediate next steps aim to maximize the benefit for PRAME-positive patients through (1) ACTengine IMA203 monotherapy at target dose, (2) combination with checkpoint inhibitors, and (3) our efficacy-enhanced next-gen TCR-T approach ACTengine IMA203CD8. In addition, we are gearing up for clinical testing of our off-the-shelf Bispecifics program, TCER IMA402 targeting PRAME, which has the potential of delivering transformational benefits for patients, combined with the advantages of easy and fast supply at significantly reduced cost of goods."

Preclinical update on next-generation ACTengine IMA203CD8
IMA203CD8 consists of IMA203-engineered T cells targeting PRAME co-transduced with CD8αβ T cell co-receptor that plays an important role during T cell antigen recognition and T cell activation. The IMA203CD8 product candidate has the potential to harness the potency of CD4 T cells. Engagement of CD4 T cells, in addition to CD8 T cells, might further enhance depth and durability of anti-tumor response and clinical outcome of TCR-T in solid cancer patients.

Immatics has exclusively licensed the CD8αβ technology from Baylor College of Medicine in Houston, Texas.
IMA203CD8 product candidate demonstrates enhanced anti-tumor activity in preclinical proof-of-concept data, which will be presented on-site at the SITC (Free SITC Whitepaper) Annual Meeting on Friday, November 12, 2021 between 7 am – 8:30 pm EST as well as virtually throughout the duration of the conference. The poster will also be available on Immatics’ website following the poster presentation.
IND submission for IMA203CD8 cohort is expected in the first half of 2022.

Further updates on the ACTengine IMA200 Programs

IMA201 (MAGEA4/A8) and IMA202 (MAGEA1)

The dose escalation Phase 1a study with ACTengine IMA201 and IMA202 product candidates directed at MAGEA4/8 and MAGEA1 HLA-A*02 peptides respectively, continue to advance with IMA202 at dose level 3 and IMA201 at dose level 2.
At data cut-off on September 17, 2021, 12 heavily pretreated patients have been treated; 8 out of 12 patients showed disease control. Tumor shrinkage was observed in 6 patients.
All treatment-emergent adverse events (TEAEs) for both IMA201 and IMA202 continue to be transient and manageable. No dose limiting toxicities (DLT) or higher grade CRS/ICANS have been observed.
The next step in the IMA201 and IMA202 trials is to complete dose escalation including target dose (DL3).
IMA204 (COL6A3 exon 6)

ACTengine IMA204 is a potential first-in-class TCR-T directed against COL6A3 exon 6, a novel tumor stroma target highly expressed in several solid cancers. IMA204 utilizes a next-generation CD8-independent TCR with full functionality in both CD4 and CD8 T cells.
IND-enabling studies are close to completion. Submission of the IND application for IMA204 is now expected in 2022 to allow accelerated initiation of the multiple ACTengine IMA203 Ph1b cohorts.
1DL2 here includes patients dosed with DL2, EC1 and EC2 (EC1: Enrichment cohort with intermediate dose level between DL1 and DL2 , EC2: between DL2 and DL3)

Immatics conference call
Immatics will host a conference call on Tuesday, November 9, 2021 at 8:30 am EST / 2:30pm CET to discuss these clinical data and the company’s comprehensive strategy to target PRAME via different programs. The webcast and presentation can be accessed directly through this link. Participants may also access the slides and the webcast on the Immatics website in the Investors section under "Presentations" at www.investors.immatics.com/events-presentations. A replay of the webcast will be made available shortly after the conclusion of the call and archived on the Company’s website for at least 90 days.

About Immatics’ PRAME Programs
Immatics’ PRAME programs 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 – such as uterine carcinoma, synovial sarcoma, melanoma, ovarian carcinoma, uveal melanoma, squamous NSCLC, breast carcinoma and HNSCC – thereby supporting the programs’ potential to address a broad cancer patient population. Immatics’ PRAME peptide demonstrates a high copy number per tumor cell and is homogenously 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, the Company has generated a highly specific T cell receptor (TCR) against this target for its TCR-based cell therapy approach, ACTengine IMA203, and its TCR Bispecifics pipeline, TCER IMA402. Both therapeutic modalities have distinct attributes and mechanisms of actions suitable for cancer patients at different disease stages and tumor types.

ACTengine IMA203 is currently being evaluated in an ongoing Phase 1a dose escalation cohort utilizing a 3+3 design with four increasing IMA203 dose levels to determine the Recommended Phase 2 Dose (RP2D). Immatics plans to expand the IMA203 study to multiple Phase 1b study cohorts including (1) IMA203 as a monotherapy, (2) IMA203 in combination with an immune checkpoint inhibitor and (3) IMA203CD8, a next-generation cell therapy where IMA203 engineered T cells are co-transduced with a CD8αβ co-receptor.

TCER IMA402 is a PRAME-specific "off-the-shelf" biologic that leverages the body’s immune system by redirecting and activating T cells towards cancer cells. TCER IMA402 has previously demonstrated anti-tumor activity against PRAME-positive cancer cells in an in vivo mouse model leading to consistent tumor regression including complete responses.

About ACTengine programs
ACTengine is a personalized 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, an approach also known as TCR-T. ACTengine programs IMA201 (NCT03247309), IMA202 (NCT03441100) and IMA203 (NCT03686124) are currently in clinical development in the US and in Germany. The objective of the three Phase 1 clinical trials is to evaluate safety, tolerability and initial signs of clinical and biological efficacy in target-positive solid cancer patients. IMA204 is currently in pre-clinical development. All ACTengine product candidates can be rapidly 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. The ACTengine IMA200 Programs are co-funded by the Cancer Prevention and Research Institute of Texas (CPRIT).