On December 3, 2020 Genmab A/S (Nasdaq: GMAB) reported that Janssen Biotech, Inc. (Janssen) submitted a Biologics License Application (BLA) to the U.S. Food and Drug Administration (U.S. FDA) seeking approval of amivantamab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy (Press release, Genmab, DEC 3, 2020, View Source [SID1234572123]). This is the first BLA submission for a product candidate that was created using Genmab’s proprietary DuoBody technology platform. In July 2012, Genmab entered into a collaboration with Janssen to create and develop bispecific antibodies using Genmab’s DuoBody technology platform.

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"Today’s milestone underscores the promise of our DuoBody technology platform to effectively create innovative and truly differentiated bispecific antibody therapeutics," said Jan van de Winkel, Ph.D., Chief Executive Officer of Genmab.

For more information related to Janssen’s amivantamab filing click here.

About Non-small Cell Lung Cancer
Lung cancer is the most common cancer worldwide. Approximately 80 to 85 percent of lung cancers are classified as NSCLC and include subtypes adenocarcinoma, squamous cell carcinoma and large cell carcinoma1,2. Mutations in the EGFR gene are common in patients with NSCLC, including 10 to 15 percent of NSCLC patients in Western countries.3,4 The five-year survival rate for all patients with metastatic NSCLC with EGFR mutations who are treated with EGFR tyrosine kinase inhibitors is less than 20 percent.5,6 In addition, the estimated median overall survival for patients with NSCLC and EGFR Exon 20 insertion mutations is shorted than in patients with common EGFR mutations.7

On December 3, 2020 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) seeking approval of amivantamab for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy (Press release, Janssen Pharmaceuticals, DEC 3, 2020, View Source [SID1234572140]). The application marks the first-ever regulatory submission for the treatment of patients with NSCLC with EGFR exon 20 insertion mutations.1 The Company has also established an expanded access program (EAP) [NCT04599712]2 for patients in the U.S. who may be eligible to obtain access to amivantamab during review of the BLA. For information about Janssen’s pre-approval access program, visit View Source

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Amivantamab is an investigational, fully-human EGFR and mesenchymal epithelial transition factor (MET) bispecific antibody with immune cell-directing activity that targets tumors with activating and resistance EGFR and MET mutations and amplifications.3,4,5,6 In March 2020, amivantamab received Breakthrough Therapy Designation from the FDA for this population.7

"This submission marks an important step forward in our drive toward evolving the treatment landscape for patients with NSCLC who have EGFR exon 20 insertion mutations and for whom there are no FDA-approved targeted treatment options," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head, Oncology, Janssen Research & Development, LLC. "We are committed to the development of therapies like amivantamab that progress precision medicine and target specific pathways, and to providing access through expanded access programs."

The BLA submission for amivantamab is based on data from the monotherapy arm of the Phase 1 CHRYSALIS study, a multi-center, open-label, multi-cohort study evaluating the safety and efficacy of amivantamab as a monotherapy and in combination with lazertinib*, a novel third-generation EGFR tyrosine kinase inhibitor (TKI)8, in adult patients with advanced NSCLC.9 In the study, investigators assessed efficacy using overall response rate per Response Evaluation Criteria in Solid Tumors Version 1.1** (RECIST v1.1), clinical benefit rate, and duration of response and progression-free survival, as well as the safety profile of amivantamab.8,10 Early data about amivantamab as a monotherapy treatment in patients with NSCLC with EGFR exon 20 insertion mutations were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2020 Virtual Scientific Program (Abstract #9512).10

"Lung cancer remains the leading cause of cancer deaths worldwide. Given this significant unmet need, we at Johnson & Johnson are committed to improving outcomes for patients diagnosed with this complex, deadly disease. With today’s submission for amivantamab, we are one step closer to that goal," said Mathai Mammen, M.D., Ph.D., Global Head, Janssen Research & Development, Johnson & Johnson. "We are steadfast in our focus to advance novel therapeutics and medicines that will transform the trajectory of some of the most challenging and deadly diseases of our time, including lung cancer."

EGFR mutations, leading to uncontrolled cancer cell growth and division11, are some of the most common mutations in NSCLC.12 EGFR exon 20 insertion mutations are the third most prevalent primary EGFR mutation.13 However, EGFR exon 20 insertion mutations are also often undetected.13 Next Generation Sequencing (NGS) is effective at detecting EGFR exon 20 insertion mutations and broader use of NGS can help to detect these mutations.14 Cancer driven by EGFR exon 20 insertion mutations is generally insensitive to approved EGFR TKI treatments and, in addition, carries a worse prognosis compared with cancer driven by more common EGFR mutations, including exon 19 deletions/L858R substitutions.15 Patients with EGFR exon 20 insertion mutations have a median survival of less than 17 months16, which is much shorter than patients with EGFR exon 19 deletions or L858R mutations, who have a median survival of 32-39 months.17

*In 2018, Janssen entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.

**RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumors respond to treatment and is based on whether tumors shrink, stay the same, or get bigger.

About Amivantamab

Amivantamab is an investigational, fully-human EGFR-MET bispecific antibody with immune cell-directing activity that targets tumors with activating and resistance EGFR mutations and MET mutations and amplifications.3,4,5,6 Amivantamab is pending regulatory review as a potential treatment for patients with NSCLC with EGFR exon 20 insertion mutations whose tumors typically do not respond to current standard of care. Companion diagnostics to identify patients with EGFR exon 20 insertion mutations have been an integral part of the development program for amivantamab. The production and development of the antibody followed Janssen Biotech, Inc.’s licensing agreement with Genmab for use of its DuoBody technology platform.

About the Amivantamab Expanded Access Program Protocol (EAP)

The amivantamab EAP is for U.S. patients 18 years of age or older who have histologically or cytologically confirmed unresectable or metastatic NSCLC with an EGFR exon 20 insertion mutations who are not amenable to curative therapy and whose disease has progressed during or after current standard of care platinum-based chemotherapy, who may benefit from treatment with amivantamab prior to its potential FDA approval.2 The EAP has specific inclusion and exclusion criteria for patients to be considered for enrollment in the program, and patients must not be eligible for another amivantamab study.2 Interested patients should contact their physician to discuss whether they may be a candidate for amivantamab through the EAP.2 Additional information about the expanded access protocol can be found on clinicaltrials.gov (NCT04599712) and at View Source

About Non-Small Cell Lung Cancer (NSCLC)

Worldwide, lung cancer is the most common cancer, and NSCLC makes up 80 to 85 percent of all lung cancers.18,19 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.19 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.11 EGFR mutations are present in 10 to 15 percent of patients with NSCLC and occur in 40 to 50 percent of Asian patients who have NSCLC adenocarcinoma.20 The five-year survival rate for all patients with metastatic NSCLC with EGFR mutations treated with EGFR TKIs is less than 20 percent.21,22 Estimated median overall survival for patients with NSCLC and EGFR exon 20 insertion mutations is shorter than in patients with common EGFR mutations.11

On December 3, 2020 Antengene Corporation Limited ("Antengene", SEHK: 6996.HK), a leading innovative biopharmaceutical company dedicated to discovering, developing and commercializing global first-in-class and/or best-in class therapeutics in hematology and oncology, reported it has submitted new drug applications ("NDA(s)") for XPOVIO (selinexor, ATG-010) to the Health Sciences Authority of Singapore and to the Australian Therapeutic Goods Administration for three indications: the treatment of adult patients with relapsed or refractory multiple myeloma ("rrMM") who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody; and in combination with bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior line of therapy; and for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma ("rrDLBCL"), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. Australian Therapeutic Goods Administration has accepted the NDA of Antengene on December 2, 2020.

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A new drug application (NDA) for XPOVIO (selinexor) has also been submitted to the Hong Kong Department of Health for the treatment of adult patients with rrMM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody.

In South Korea, XPOVIO (selinexor) has been granted orphan drug designation for the treatment of adult patients with rrMM who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody and for the treatment of adult patients with rrDLBCL, not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy.

XPOVIO (selinexor, ATG-010) is a first-in-class and only-in-class oral selective inhibitor of nuclear export, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ: KPTI). In July 2019, the US Food and Drug Administration (FDA) approved XPOVIO (selinexor) in combination with low-dose dexamethasone for the treatment of rrMM. After its initial approval of rrMM, FDA approved XPOVIO (selinexor) as a single-agent for the treatment of rrDLBCL in June 2020.

In November 2020, at the Connective Tissue Oncology Society 2020 Annual Meeting (CTOS 2020), Antengene’s partner, Karyopharm Therapeutics, presented positive results from the Phase 3 portion of the randomized, double blind, placebo controlled, cross-over SEAL study evaluating single agent, oral XPOVIO (selinexor) versus matching placebo in patients with liposarcoma. Karyopharm also recently announced that the ongoing phase 3 SIENDO study of XPOVIO (selinexor) in patients with endometrial cancer passed planned interim futility analysis and that Data and Safety Monitoring Board (DSMB) recommended the study should proceed as planned without any modifications. Top-line SIENDO study results are expected in the second half of 2021.

About XPOVIO

XPOVIO is a first-in-class and only-in-class oral selective inhibitor of nuclear export compound, developed by Antengene and Karyopharm Therapeutics Inc. (NASDAQ: KPTI). In July 2019, the US Food and Drug Administration (FDA) approved XPOVIO in combination with low-dose dexamethasone for the treatment of relapsed or refractory multiple myeloma (rrMM) and in June 2020 approved XPOVIO as a single-agent for the treatment of relapsed or refractory diffuse large B-cell lymphoma (rrDLBCL). XPOVIO is so far the first and only oral SINE compound approved by the FDA. XPOVIO is also being evaluated in several other mid-and later-phase clinical trials across multiple solid tumor indications, including liposarcoma and endometrial cancer.

Antengene is conducting two registrational Phase 2 clinical trials of XPOVIO in China for relapsed refractory multiple myeloma (MARCH) and for relapsed refractory diffuse large B-cell lymphoma (SEARCH), and has initiated clinical trials for high prevalence cancer types in the Asia Pacific region including peripheral T-cell lymphoma and NK/T-cell lymphoma (TOUCH) and KRAS-mutant non-small cell lung cancer (TRUMP).

On December 2, 2020 Puma Biotechnology, Inc. (NASDAQ: PBYI), a biopharmaceutical company, reported that it has prevailed in final appeal proceedings brought against its licensed European patent EP Patent 1848414, which covers the use of irreversible EGFR inhibitors in treating gefitinib and/or erlotinib resistant cancer and cancer with a T790M EGFR mutation (Press release, Puma Biotechnology, DEC 2, 2020, View Source [SID1234572097]). The European Board of Appeals announced its decision at a hearing on December 1st, rejecting the opposition of EP Patent 1848414 initiated by a Boehringer Ingelheim entity.

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The EP Patent 1848414 originally granted in April 2011 covers the use of irreversible EGFR inhibitors in treating gefitinib and/or erlotinib resistant cancer and cancer with a T790M EGFR mutation. On November 28, 2011, an opposition was filed seeking invalidation of the patent. The Opposition Division of the European Patent Office issued a decision on February 4, 2014 revoking some claims but upheld a subset of the granted claims relating to a pharmaceutical composition for use in treating cancer in a subject having a T790M EGFR mutation without any modification. Both parties appealed that decision in 2017. At a final hearing, the Board of Appeals announced its decision, concluding that the opposition was inadmissible and reversing the European Opposition Division decision issued in 2014, thereby upholding the EP Patent 1848414 as originally granted.

On December 2, 2020 Immatics N.V. (NASDAQ: IMTX; "Immatics"), a clinical-stage biopharmaceutical company active in the discovery and development of T cell redirecting cancer immunotherapies, reported financial results and provided a business update for the quarter ended September 30, 2020 (Press release, Immatics, DEC 2, 2020, View Source [SID1234572076]).

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"The third quarter was highlighted by meaningful progress in our ACTengine IMA200 clinical trial series. Seven clinical sites in Germany and the US are now initiated and screening patients. These advancements mark critical steps towards delivering our clinical milestones for the coming year including reporting on initial data for ACTengine patients in dose escalation in Q1," said Harpreet Singh, Ph.D., CEO of Immatics. "In conjunction with our clinical and operational progress, we are pleased to further strengthen the Company’s capabilities with the appointments of both Eliot Forster to the Board and Arnd Christ as Chief Financial Officer."

Third Quarter 2020 and Subsequent Company Progress

Adoptive Cell Therapy Programs

ACTengine IMA200 Series – Immatics continued to select and initiate additional clinical trial sites in Germany and the US. The increased patient enrollment seen at sites in Germany was able to mitigate the impact of the global COVID-19 pandemic at US sites. These patients are expected to be treated within the fourth quarter this year, moving Immatics towards delivering the clinical milestones for ACTengine in the coming year. Combined initial data readout for ACTengine programs, IMA201, IMA202 and IMA203, continues to be expected in Q1 2021. Reported initial data will focus on safety and pharmacodynamic data including engraftment level, persistence and molecular phenotype of infused T cells as well as clinical change of target tumor lesions.
ACTengine IMA204 – Immatics presented preclinical data from the ACTengine cell therapy program targeting the tumor microenvironment on September 10. IMA204 is directed at a novel target, COL6A3 exon 6, which is highly expressed in the tumor stroma of a variety of solid cancers. An affinity-enhanced TCR candidate directed to this target demonstrated full functionality in CD8+ and CD4+ T cells indicating that this TCR could be employed in a next-generation ACTengine approach without the need of CD8 co-receptor transduction. Submission of an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA) for IMA204 remains anticipated for 2021.
ACTolog IMA101 – On November 10, Immatics presented topline data from its clinical pilot trial IMA101, a personalized multi-target ACT approach using the patient’s own, non-engineered T cells. The trial demonstrated feasibility and tolerability of this approach as well as very high persistence of endogenous T cells directed against defined pHLA targets. Clinical course observations in patients treated with T cells directed at the tumor stroma target COL6A3 exon 6 warrant further exploration of this target within ACTengine. The results also support further development of a multi-target approach using multiple engineered TCRs simultaneously in ACTengine.

TCR Bispecifics Programs

IMA401 – A preclinical data update from Immatics’ first TCR Bispecifics (TCER) program on October 29, delivered pre-clinical proof-of-concept for IMA401 demonstrating complete remission of transplanted human tumors in mice as well as favorable CMC characteristics. The IMA401 cancer target, an HLA-A*02-bound peptide derived from both MAGEA4 and MAGEA8, showed more than 5-fold higher target copy numbers per tumor cell than a commonly used target peptide derived from MAGEA4. Submission of the IMA401 IND/IMPD application remains expected by the end of 2021.
Corporate Development

Management and Board of Directors Updates

Eliot Forster, Ph.D., joined Immatics’ Board of Directors as a new member in September 2020. He brings to Immatics extensive experience, including leadership of trailblazing biopharmaceutical companies in the field of immuno-oncology as well as other therapeutic areas.
In October 2020, Arnd Christ joined Immatics’ leadership team as Chief Financial Officer (CFO). He was previously the CFO of Nasdaq-listed InflaRx and brings nearly two decades of experience serving as the CFO of both private and public biotechnology companies.

Collaborations and Strategic Alliances

On August 6, Immatics announced the extension of its strategic alliance with UTHealth. The continued collaboration will provide Immatics exclusive access to three cGMP suites enabling manufacturing and supply of its ACT products for current and upcoming Phase 1 clinical trials in the US and Europe for an additional four years until end of 2024.

Third Quarter 2020 Financial Results

Cash Position: Cash and cash equivalents as well as other financial assets sum up to €259.3 million ($303.6 million1) as of September 30, 2020 compared to €86.1 million ($100.8 million1) as of June 30. The increase is mainly due to the business combination with ARYA Sciences Acquisition Corporation completed in July 2020 (ARYA merger) and the concurrent PIPE Financing.

Revenue: Total revenue, consisting of revenue from collaboration agreements, was €7.8 million ($9.1 million1) for the three months ended September 30, 2020, compared to €5.1 million ($6.0 million1) for the three months ended September 30, 2019.

Research and Development Expenses: R&D expenses were €17.5 million ($20.5 million1) for the three months ended September 30, 2020, compared to €10.2 million ($11.9 million1) for the three months ended September 30, 2019. The increase is mainly due to increased share-based compensation (€4.6 million; $5.4 million1).

General and Administrative Expenses: G&A expenses were €9.2 million ($10.8 million1) for the three months ended September 30, 2020, compared to €2.7 million ($3.2 million1) for the three months ended September 30, 2019. The increase is mainly due to increased share-based compensation (€3.6 million; $4.2 million1) as well as one-time transaction costs of the NASDAQ listing in connection with the ARYA merger in July.

Net Loss: Net loss was €177.1 million ($207.3 million1) for the three months ended September 30, 2020, compared to €5.0 million ($5.9 million1) for the three months ended September 30, 2019 of which €152.8 million ($178.9 million1) resulted from a one-time, non-cash expense in connection with the ARYA merger. The main part of this €152.8 million ($178.9 million1) non-cash expense resulted from the share price increase between signing and closing of the ARYA merger. For detailed information, please refer to Note 9 of the Notes to the Financial Statements.

Upcoming Investor Conferences

Piper Sandler Healthcare Conference – December 1-3, 2020
10th Annual SVB Leerink Global Healthcare Conference – February 24-26, 2021

To see the full list of events and presentations, visit www.investors.immatics.com/events-presentations.

Full financial statements can be found in the current report on Form 6-K filed with the Securities and Exchange Commission (SEC) and published on the SEC website under View Source

1 All amounts translated using the exchange rate published by the European Central Bank in effect as of September 30, 2020 (1 EUR = 1.1708 USD).