On July 26, 2022 Sirnaomics Ltd. (the "Company" or "Sirnaomics", stock code: 2257.HK), a leading biopharmaceutical company in discovery and development of RNAi therapeutics, reported that the Company has received regulatory clearance from the Taiwan Ministry of Health and Welfare (TMHW) of its Investigational New Drug (IND) application to commence a Phase I trial of STP705, siRNA (small interfering RNA) drug candidate, for the treatment of patients with advanced liver tumors (Press release, Sirnaomics, JUL 26, 2022, View Source [SID1234616974]).

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The Phase I multicenter, open-Label, dose escalation study in Taiwan is part of a global study of STP705 designed to evaluate the safety, tolerability, pharmacokinetics, and anti-tumor activity. STP705 is administered intratumorally for cholangiocarcinoma, hepatocellular carcinoma, or liver metastases in subjects with advanced/metastatic or surgically unresectable solid tumors who are refractory to standard therapy. The study was started in the United States in March 2021, and the study in Taiwan is expected to begin enrolling in the coming months.

"The IND green light in Taiwan for STP705 represents a major milestone for the Company’s expansion of its clinical studies into Asia," said Dr. Patrick Lu, founder, chairman of the Board, Executive Director, President and CEO of Sirnaomics. "We believe that the study results in Taiwan will strengthen the body of data in a multicenter global trial, which will also include a future study in the mainland China. Sirnaomics is currently in a strong position to lead the way in RNAi therapeutics for the development of novel oncology therapies."

"This IND approval will allow more opportunities to manage critical diseases such as liver cancer with high unmet clinical need in Taiwan and the region," stated Steven Long, Ph.D. Sirnaomics Chief Development Officer. "Taiwan’s regulatory bodies and clinical testing hospitals are well known for meeting international standards. We expect to conduct more oncology clinical studies in Asia-Pacific regions in the coming years."

About STP705

STP705 is composed of two siRNA oligonucleotides, targeting TGF-β1 and COX-2 mRNA respectively, formulated in nanoparticles with a Histidine-Lysine Co-Polymer (HKP) peptide as the carrier. Each individual siRNA was demonstrated to inhibit the expression of the target mRNA, and combining the two siRNA’s produces a synergistic effect that diminishes pro-inflammatory factors. Over-expressions of TGF-β1 and COX-2 have been well-characterized in playing key regulatory roles in tumorigenesis.

On July 26, 2022 Valo Therapeutics Oy (ValoTx), the developer of novel, adaptable immunotherapy platforms for cancer and infectious diseases, reported the exclusive licensing of intellectual property rights (IPR) from the University of Helsinki, Finland, for the institution’s innovative PeptiCHIP technology (Press release, Valo Therapeutics, JUL 26, 2022, View Source [SID1234616973]). Following further validation by ValoTx, and the achievement of specific milestones, the IPR will transfer in full to the company. This is a strategically important addition for the company as it will enable the rapid identification of tumour antigens for the development of new cancer immunotherapies using Valo’s existing technologies and opens the possibility for a tumor specific personalized approach in the future. In addition, due to the advantages PeptiCHIP offers in comparison to existing antigen identification approaches, ValoTx expects to be able to commercialise the technology through creating a revenue-generating business unit.

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Paul Higham, CEO of ValoTx, commented, "Precisely knowing the antigen profile of a tumor is crucial in developing new and effective immunotherapies in the treatment of cancer and particularly so when developing a personalized approach. PeptiCHIP enables us to identify these antigens faster than existing technologies and, in combination with our lead delivery platform, PeptiCRAd, we see significant potential for the development of personalized cancer immunotherapies across a wide range of cancers both for our partners and in-house programmes."

The PeptiCHIP technology consists of a microfluidic chip for identification of neoantigens, coupled with a software algorithm that identifies immunogenic peptides. Together, the device and software form an easy-to-use lab tool that enables the fast and accurate identification of tumor antigen profiles.

Dr Sari Pesonen, CSO of ValoTx, added, "This is another successful IP acquisition from our long-standing innovation partnership with the University of Helsinki. PeptiCHIP technology opens new avenues for partnerships and our in-house programmes focused on new and personalized immunotherapies for the treatment of cancer."

The PeptiCHIP technology is expected to facilitate neoantigen identification at a lower cost and requiring less tumor material compared to current methods. This should lead to faster tumor antigen identification in standard biopsy clinical workflows.

Helsinki Innovation Services Ltd, an innovation and commercialization company owned by the University of Helsinki, managed the intellectual property rights for PeptiCHIP and the commercial negotiations with ValoTx.

On July 26, 2022 WuXi AppTec (stock code: 603259.SH / 2359.HK), a global company that provides a broad portfolio of R&D and manufacturing services that enable companies in the pharmaceutical, biotech and medical device industries to advance discoveries and deliver groundbreaking treatments to patients, reported its financial results for the first half of the year ending June 30, 2022 ("Reporting Period") (Press release, WuXi AppTec, JUL 26, 2022, View Source [SID1234616972]).

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This release provides a summary of the results and is not intended to be a comprehensive report. For additional information, please refer to the 2022 Interim Report and other relevant announcements published on the websites of the Shanghai Stock Exchange (www.sse.com.cn) and the Stock Exchange of Hong Kong (www.hkexnews.hk), and the designated media for dissemination of the relevant information. Investors are advised to exercise caution and be aware of the investment risks in trading Company shares.

All financial information disclosed in this press release is prepared based on International Financial Reporting Standards (IFRS), in currency of RMB.

The 2022 First-Half Report of the Company has not been audited.

[1] In the first half of 2021 and 2022, WuXi AppTec had a fully-diluted weighted average share count of 2,924,395,370 and 2,951,897,466 ordinary shares, respectively.

First-Half 2022 Financial Highlights

Revenue grew 68.5% year-over-year to RMB17,756 million. This is primarily attributable to the Company’s continued focus on leveraging its unique Contract Research, Development and Manufacturing Organization (CRDMO) business model to achieve synergy and strong growth across our business segments:

WuXi Chemistry revenue grew 101.9% to RMB12,974 million and adjusted non-IFRS gross profit grew 94.3% to RMB5,314 million, with a gross profit margin of 41%.
WuXi Testing revenue grew 23.6% to RMB2,605 million and adjusted non-IFRS gross profit grew 26.1% to RMB927 million, with a gross profit margin of 35.6%.
WuXi Biology revenue grew 18.5% to RMB1,091 million and adjusted non-IFRS gross profit grew 30.7% to RMB444 million, with a gross profit margin of 40.7%.
WuXi ATU revenue grew 35.7% to RMB615 million and adjusted non-IFRS gross profit was RMB(43) million, with a gross profit margin of -6.9%.
WuXi DDSU revenue declined 26.7% to RMB455 million and adjusted non-IFRS gross profit declined 52.4% to RMB140 million, with a gross profit margin of 30.7%.
Unit: RMB million

Note:

1. Adjusted Non-IFRS Gross Profit of WuXi ATU was RMB(42.74) million in the first half of 2022, compared
to RMB(3.41) million in the first half of 2021, decreased by RMB(39.34) million.

2. Any sum of the data above that is inconsistent with the total is due to rounding.

IFRS gross profit increased 65.5% year-over-year to RMB6,427 million. Gross profit margin was 36.2%.[2]
Adjusted Non-IFRS gross profit increased 65.5% year-over-year to RMB6,790 million. Adjusted Non-IFRS gross margin was 38.2%.
EBITDA increased 64.4% year-over-year to RMB6,483 million.
Adjusted EBITDA increased 66.6% year-over-year to RMB6,077 million.
Net profit attributable to owners of the Company increased 73.3% year-over-year to RMB4,636 million.
Adjusted non-IFRS net profit attributable to owners of the Company increased 75.7% year-over-year to RMB4,301 million.
Diluted EPS increased 62.6% year-over-year to RMB1.48, while adjusted diluted non-IFRS EPS increased by 73.8% year-over-year to RMB1.46.
[2] If prepared under Accounting Standard for Business Enterprises of PRC, the gross profit grew 65.2% year-over-year to RMB 6,437 million. Gross profit margin was 36.3%.

First-Half 2022 Business Highlights

– In the first half of 2022, demand for our services was strong and we grew our customer base to more than 5,850 active accounts by adding over 650 new customers. We continued to optimize cross-platform synergies to better serve our customers worldwide, strengthen our unique competitive advantage as a fully integrated CRDMO (Contract Research, Development and Manufacturing Organization) and CTDMO (Contract Testing, Development and Manufacturing Organization), and provide one-stop services for our clients from discovery to development and manufacturing. Revenue growth was demonstrated across our expanding global customer base:

Revenue from US-based customers grew 104% to RMB11,909 million; revenue from Europe-based customers grew 24% to RMB1,853 million; revenue from China-based customers grew 27% to RMB3,175 million; and revenue from other regions grew 15% to RMB819 million.
We continued to expand our customer base and retain existing clients. During the Reporting Period, revenue from existing clients grew 79% to RMB17,366 million and new clients contributed RMB391 million in revenue.
During the Reporting Period, revenue from the top 20 global pharmaceutical companies grew 165%, up to RMB7,856 million; revenue generated from all other customers grew 31% to RMB9,900 million.
Our unique positioning across the pharmaceutical development value chain drove our "follow-the-customer" and "follow-the-molecule" strategies and enhanced synergies across our business segments. Customers using services from multiple business units contributed RMB15,744 million in revenue, growing 82% year-over-year.
– WuXi Chemistry: CRDMO integrated business model drives revenue to double

Revenue grew 101.9% to RMB12,974 million and adjusted non-IFRS gross profit grew 94.3% to RMB5,314 million, with a gross margin of 41.0%. Excluding COVID-19 commercial projects, WuXi Chemistry revenue grew 36.8%.
Revenue from small molecule discovery services ("R") grew 36.5% to RMB3,504 million.
i. Our industry-leading small molecule drug discovery platform delivered more than 180,000 custom synthesized compounds to our clients in first half 2022. Through our small molecule discovery services, we enabled our customers to accelerate their research while generating opportunities for our downstream business units. As part of our "follow the customer" and "follow the molecule" strategies, we established trusted partnerships with our global customers, which supported the rapid and sustainable growth of our CRDMO business.
ii. We continued executing our "long-tail" strategy, and those customers continue to have strong demands for our discovery services in small molecules, oligonucleotides and peptides.
Revenue from our small molecule development and manufacturing (D&M) service grew 145.4% to RMB9,470 million.
i. During the Reporting Period, the Company added 473 new molecules to our D&M pipeline funnel for a total of 2,010 molecules, including 43 in commercial stage, 52 in phase III, 288 in phase II and 1,627 in phase I and pre-clinical stages.
ii. D&M services for new modalities is also gaining strong momentum. During the reporting period, the number of oligonucleotide and peptide D&M clients increased 123% to 98, and the number of oligonucleotide and peptide molecules increased 63% to 142. Revenue from oligonucleotide and peptide D&M reached RMB705 million.
Capacity expansion of WuXi Chemistry continued to accelerate in the first half of 2022 to meet demands. In June 2022, we announced the opening of another high-potency API plant at our Changzhou site. The new plant will meet growing demand for high-potency API process R&D and manufacturing services. In July 2022, we announced the opening of a new large-scale oligonucleotide and peptide manufacturing facility at our Changzhou campus. The new facility underscores our ongoing commitment to enhancing our capacity and capability to meet the fast-growing customer needs for oligonucleotide and peptide therapeutics development and manufacturing worldwide. In addition, we opened a continuous manufacturing (flow chemistry) plant at our Changzhou campus for large-scale API and advanced intermediate production. This new expansion marks our ongoing effort to enhance our flow chemistry platform in response to increasing customer demand for safe and sustainable pharmaceutical manufacturing.
– WuXi Testing: strong growth in lab testing services

Revenue from WuXi Testing grew 23.6% to RMB2,605 million and adjusted non-IFRS gross profit grew 26.1% to RMB927 million, with a gross margin of 35.6%.
Revenue from lab testing services grew 34.6% year-over-year to RMB1,890 million.
i. The Company provides a full range of laboratory testing services to our customers, including DMPK (drug metabolism and pharmacokinetics), toxicology, and bioanalysis for drug development testing as well as medical device testing. We leveraged our integrated WuXi AppTec Investigational New Drug (IND) program (WIND) to generate preclinical data and prepare global regulatory submissions of IND packages, expediting the IND application process for many customers worldwide. Customers signed 72 WIND service packages with us in the first half of 2022.
ii. Drug safety evaluation services achieved strong revenue growth of 53% year-over-year. We maintained our industry-leading position in Asia for drug safety evaluation services that meet global regulatory requirements.
iii. Our largely US-based medical device testing business has turned around and grew 31% year-over-year.
Revenue growth of 1.7% from clinical CRO & SMO (Site Management Organization) slowed down significantly, mainly due to Covid-19 Omicron variants outbreak in many cities in China during the second quarter of 2022.
i. For clinical CRO, the Company provided services to 170 projects, enabling our customers to obtain 10 IND approvals.
ii. For SMO, the Company continued its rapid expansion. Our SMO maintained more than 4,600 staff in around 150 cities in China, providing services in more than 1,000 hospitals. The team size increased 16% year-over-year, demonstrating strong demand for our SMO services. In the first half of 2022, SMO supported our clients for 16 new drug approvals.
– WuXi Biology: new modalities-related biology services drive growth

Revenue from WuXi Biology grew 18.5% to RMB1,091 million and adjusted non-IFRS gross profit grew 30.7% to RMB444 million, with a gross margin of 40.7%.
The Company has the largest discovery biology enabling platform, with more than 2,500 experienced scientists who provide comprehensive biology services covering all stages and therapeutic areas of drug discovery. The Company has established 3 centers of excellence for non-alcoholic steatohepatitis (NASH), anti-viral, neuroscience & aging.
The Company has a leading DNA Encoded Library (DEL) and compound generation platform, providing services for more than 1,200 customers globally. We leverage our global network across Asia, Europe and North America, to develop and use new technologies such as OBOC ("One-Bead-One-Compound") to drive growth.
The Company continues to build new biology capabilities related to new modalities, including target protein degradation, nucleic acid-based and conjugated modalities, vector platform, and novel drug delivery vehicles. During the Reporting Period, WuXi Biology revenue from new modalities and large molecules grew 67%, and its revenue contribution rose to 19.0% in the first half of 2022 from 14.6% in 2021, suggesting that new modalities-related biology services have become an increasingly important growth driver.
– WuXi ATU: CTDMO business model drives growth

Revenue from WuXi ATU grew 35.7% year over year to RMB615 million and adjusted non-IFRS gross profit was RMB(43) million, with a gross margin of -6.9%. Gross profit declined largely due to under-utilized capacities of the newly built Shanghai Lingang site. With capacity utilization ramping up in the coming quarters, gross profit is expected to turn positive and improve.
During the Reporting Period, the Company focused on improving our CTDMO integrated enabling platform and strengthened testing services, capabilities, and capacities. We provided development and manufacturing services for 67 projects, including 51 pre-clinical and Phase I projects, 9 Phase II projects, and 7 Phase III projects (4 projects are in BLA preparation stage).
The Company announced the launch of Tetracycline-Enabled Self-Silencing Adenovirus (TESSA) in March 2022. TESSA technology is a revolutionary and novel process for transfection-free, scalable manufacturing of adeno-associated virus (AAV). Process now scaled to 200L that produces more than 10 times AAV products compared to traditional plasmid-based manufacture. At the end of the first half of 2022, we had 30 TESSA evaluation projects by customers.
– WuXi DDSU: business evolving to focus on innovative drug discovery services

Revenue from WuXi DDSU declined 26.7% to RMB455 million and adjusted non-IFRS gross profit declined 52.4% to RMB140 million, with a gross margin of 30.7%. DDSU’s revenue decline was mainly attributed to business evolution that aim to better serve the growing needs of clients in China for novel and innovative products, which will take longer to deliver INDs.
During the first half of 2022, our success-based drug discovery service unit filed INDs for 9 drug candidates and obtained 19 CTAs on behalf of China-based customers. As of June 30, 2022, we have cumulatively submitted 153 new chemical entity IND filings with the NMPA and obtained 129 CTAs, with 1 project in NDA review stage, 5 projects in Phase III clinical trials, 18 projects in Phase II clinical trials, and 77 projects in Phase I clinical trials. Upon these products’ successful launch to the market by our customers, we will begin receiving royalty income.
We are now putting our efforts towards the discovery of potential best-in-class molecules and new modalities molecules for customers. In the first half of 2022, we worked for customers on 15 pre-clinical projects in new modalities that include Peptide/Peptide-Drug-Conjugation (PDC), protein degraders and oligonucleotides. Several of these projects are expected to file an IND in late 2022 or early 2023.
Our commitment to ESG

As an innovation enabler, a trusted partner, and a contributor to the global healthcare industry, WuXi AppTec Co., Ltd. ("WuXi AppTec", or "we") is committed to environmental protection and sustainability, and to be a good global corporate citizenship.

In the first half of 2022, WuXi AppTec was recognized as a "Top Rated" ESG company by Sustainalytics, a leading ESG research, ratings and data firm. In the same assessment, WuXi AppTec was placed in the top four percent of companies in the global pharmaceutical industry with a "Low Risk" of experiencing material financial impacts due to ESG factors.

We continuously strengthen sustainability management and technologies, and actively build green chemical technology platforms such as biocatalysis, flow chemistry and direct isolation. In the first half of 2022, our energy consumption intensity, carbon emission intensity and water use intensity reduced by 18.8%, 22.5% and 23.6%, respectively, as compared to that of 2021.

Management Comment

Dr. Ge Li, Chairman and CEO of WuXi AppTec, said, "We achieved record growth in the first half of 2022. Our revenue increased 68.5% year-over-year and our adjusted Non-IFRS net profit increased 75.7% year-over-year. WuXi AppTec’s performance during the first half of 2022 underscores that our unique CRDMO and CTDMO business models continue to drive rapid growth for our company and allow us to better serve customers worldwide."

"After Shanghai experienced an Omicron outbreak in the second quarter, we effectively implemented our business continuity plan and leveraged our global capacities and comprehensive capabilities to ensure the health of our employees and continue our business operations. Since June 1st, we have resumed operations of our facilities in Shanghai, and continue to meet project delivery timelines and capture new business opportunities. We have increased our revenue growth target for year end 2022 to the range of 68-72% from 65-70% year-over-year, and we are confident to deliver strong growth in 2022 and beyond."

"We have made good progress in achieving excellent results in ESG. Looking forward, we remain committed to ‘doing the right thing and doing it right.’ We will continue to focus on delivering our ESG commitments and ensuring that ESG remains a priority across our business operations today and in the future."

On July 26, 2022 As part of its ongoing efforts to address disparities in underrepresented communities, Sanofi reported a collaboration with Howard University College of Pharmacy for a two-year post-professional Doctorate in Pharmacy fellowship program (Press release, Sanofi, JUL 26, 2022, View Source [SID1234616971]). Sanofi’s goal is to hire fellows into permanent full-time positions at the company, marking the first time a Howard University College of Pharmacy industry partner has committed to post-fellowship employment.

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Set to begin in the second half of 2022, the program will award ten PharmD graduate students an opportunity to participate in practical learning experiences across multiple research and development fields, including oncology, rare diseases, neurology, immunology, regulatory, pharmacovigilance, clinical and operations, as well as US medical, public policy and patient advocacy.

John Reed, MD., Ph.D.
Global Head of Research and Development at Sanofi
"At Sanofi, we recognize that work-force diversity correlates strongly with creativity, successful problem solving, and visionary innovation. This collaboration with Howard University will allow us the opportunity to foster the next generation of scientists from historically underrepresented communities. We look forward to working with the fellows as they begin their training and become Sanofi team members who will undoubtedly help contribute to frontier innovations as we bring the next generation of life-saving medicines to patients worldwide."

Sanofi employees represent the variety of Sanofi’s patients, customers and partners, which builds a better understanding of needs and forges stronger connections. An inclusive culture unleashes our potential, increases innovation, improves our products and makes us better all around. For example, by facilitating the increased participation of diverse populations in clinical trials, Sanofi is striving to aid in the improvement of social equity and human health. With these beliefs and ambitions, the company is honored is to begin this collaboration with Howard University College of Pharmacy. The fellows’ contributions will help to bolster Sanofi’s mission and our diverse top-tier talent pipeline, and empower scholars to pursue STEM research in the future.

Anthony K. Wutoh, Ph.D., R.Ph.,
Howard University Provost and Chief Academic Officer
"We look forward to the partnership with Sanofi, a global leader in healthcare innovation, and the launch of this unique fellowship program. Howard University is among the nation’s largest producers of African-American students who complete doctorates in science, technology, engineering, and physical sciences. The Sanofi fellowship will allow promising graduates to gain real-world experience while contributing to a field that has historically overlooked and undervalued people of color."

The fellowship program with Howard University College of Pharmacy is part of Diversity, Equity & Inclusion (DE&I) strategy, which set new objectives in June 2021 to be achieved by 2025. The strategy is built around three key pillars: building representative leadership, creating a work environment where employees can bring their whole selves and engaging with the company’s diverse communities. Earlier this year, Sanofi took additional steps forward in its DE&I strategy by introducing a DE&I Board, joining the Novartis Beacon of Hope program, and fostering the creation of Global Employee Resource Groups framework.

On July 26, 2022 The Janssen Pharmaceutical Companies of Johnson & Johnson reported new data from the Phase 1b/2 CHRYSALIS-2 study (NCT04077463) cohort evaluating the safety and tolerability of the combination of RYBREVANT (amivantamab-vmjw) with the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) lazertinib and platinum-based chemotherapy (carboplatin and pemetrexed) in patients with relapsed/refractory non-small cell lung cancer (NSCLC) and EGFR mutations (Press release, Johnson & Johnson, JUL 26, 2022, View Source [SID1234616970]).1 These findings and additional updates, including data on RYBREVANT in combination with lazertinib in the frontline setting for patients with NSCLC will be presented at the IASLC 2022 WCLC hosted by the IASLC August 6-9 in Vienna, Austria.

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CHRYSALIS-2 (NCT04077463) is an ongoing clinical trial evaluating RYBREVANT in combination with lazertinib in patients with advanced NSCLC with EGFR exon 19 deletion mutations or L858R activating mutations.2 One cohort of CHRYSALIS-2 evaluates the combination of RYBREVANT and lazertinib with carboplatin and pemetrexed.1 Results from the RYBREVANT, lazertinib, carboplatin and pemetrexed combination cohort (n=20) will be featured in a mini oral presentation (Abstract #MA07.04) at the IASLC 2022 WCLC.1 Enrolled participants received a median of two prior lines of therapy.1 Prior therapies included osimertinib (n=14), gefitinib (n=3), afatinib (n=3), and platinum-based chemotherapy (n=5), among others.1

After a median follow-up of 7.1 months, the combination of RYBREVANT and lazertinib with carboplatin and pemetrexed yielded an overall response rate (ORR) of 50 percent (95 percent confidence interval [CI];27-73), with 15 out of 20 patients remaining on treatment.1 The observed safety profile of this treatment combination was consistent with the previously reported safety profile of each individual agent; no evidence of new safety signals or additional toxicity was observed.1 The most common treatment-emergent adverse events (AEs) included neutropenia (85 percent), rash (75 percent), infusion-related reaction and stomatitis (60 percent), fatigue and paronychia (50 percent each), and thrombocytopenia and nausea (40 percent each).1

"Patients with relapsed/refractory non-small cell lung cancer with EGFR mutations currently have few treatment options. For them, the promise of precision medicine has the potential to change the trajectory of their disease," said Alexander Spira, M.D., Ph.D., FACP, CEO and Clinical Director of NEXT Oncology Virginia and study investigator.‡ "The data we’ve seen with the combination of amivantamab with lazertinib and chemotherapy further demonstrate the potential of this treatment regimen for these patients, and we are optimistic about future study to improve outcomes for those with EGFR-positive non-small cell lung cancer."

Janssen is currently recruiting patients for the Phase 3 MARIPOSA-2 (NCT04988295) study to evaluate the combination of RYBREVANT and lazertinib with platinum-based chemotherapy in patients with EGFR-mutated NSCLC after disease progression on or after osimertinib.3

Separately, updated data from the frontline, treatment-naïve cohort of the Phase 1 CHRYSALIS study (NCT02609776) will be featured in a poster presentation (Abstract #P1.16-01).4 CHRYSALIS is an ongoing study evaluating the safety, pharmacokinetics and preliminary efficacy of RYBREVANT as a monotherapy and in combination, including with lazertinib, in patients with advanced NSCLC with various EGFR mutations.5 Patients enrolled in the treatment-naïve cohort had NSCLC characterized by either an EGFR exon 19 deletion (n=11) or L858R mutation (n=9), with 50 percent having co-mutations in the TP53 gene.4 All 20 patients had confirmed response (ORR of 100%). After a median follow-up of 22.3 months, 14 patients (70 percent) were progression free and remained on therapy with median duration of response and median progression-free survival not reached.4 Two patients with L858R mutations remained on treatment after their disease progressed.4 Based upon the last data cutoff on June 1, 2022 (median follow-up and treatment duration of 28 months), 12 patients (60 percent; 9 exon 19 deletion, 3 exon 21 L858R) remain progression free and on treatment.4

The safety profile of the combination of RYBREVANT and lazertinib was consistent with previous reports, and no new safety signals were identified.4 Treatment-related AEs of Grade ≥3 severity occurred in seven patients (35 percent).4 Treatment-related AEs leading to dose reduction of either RYBREVANT or lazertinib occurred in seven patients, most commonly due to rash (n=5).4 One patient had a treatment-related AE of interstitial lung disease which led to treatment discontinuation.4 Janssen is evaluating the combination of RYBREVANT and lazertinib in the frontline setting for patients with EGFR-mutated NSCLC in the ongoing Phase 3 MARIPOSA study (NCT04487080).6

"Janssen’s presence at this year’s World Conference on Lung Cancer is a testament to our continuous effort to improve outcomes for people with non-small cell lung cancer, especially those whose disease is characterized by specific genetic mutations and who tend to be underserved by the current standard of care," said Joshua Bauml, M.D., Executive Medical Director, Janssen Research & Development, LLC. "We are committed to evaluating the potential of combination regimens in delaying disease progression in the treatment-naïve setting and addressing the ongoing challenge of treatment resistance in patients with relapsed/refractory disease."

Janssen will also share data that highlight the utility of next-generation sequencing (NGS) testing in identifying patients with NSCLC who may benefit from targeted treatment in a mini oral presentation (Abstract #MA12.05).7 Results showed that compared with single-gene testing strategies, NGS testing resulted in a higher percentage of identified mutations, a shorter time to appropriate targeted therapy and lower total testing costs per patient.7

About RYBREVANT
RYBREVANT (amivantamab-vmjw) received accelerated approval by the U.S. Food and Drug Administration (FDA) in May 2021 for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.8 This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. RYBREVANT has also received approval from health authorities in Europe, as well as other markets around the world.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Non-Small Cell Lung Cancer* prefer NGS-based strategies over PCR-based approaches for the detection of EGFR exon 20 insertion variants and include amivantamab-vmjw (RYBREVANT) as a subsequent therapy option with a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.9†^

RYBREVANT is being studied in multiple clinical trials, including for untreated advanced EGFR-mutated NSCLC in the Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT in combination with lazertinib as an alternative to osimertinib for frontline treatment; the Phase 3 MARIPOSA-2 (NCT04988295) study to evaluate the combination of RYBREVANT and lazertinib with platinum-based chemotherapy in patients with EGFR-mutated NSCLC after disease progression on or after osimertinib; the Phase 1/1b CHRYSALIS-2 (NCT04077463) study assessing the combination of RYBREVANT and lazertinib in patients who have progressed after treatment with osimertinib and chemotherapy; the Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT in combination with carboplatin-pemetrexed versus chemotherapy alone in patients with advanced or metastatic EGFR-mutated NSCLC and exon 20 insertion mutations; and the Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous (SC) administration of RYBREVANT based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for RYBREVANT SC delivery.2,3,5,6,10,11

*NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

†See the NCCN Guidelines for detailed recommendations, including other treatment options.10

^The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.

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About Lazertinib
Lazertinib is an oral, third-generation, brain-penetrant, EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR.12 Interim safety and efficacy results from the lazertinib Phase 1/2 study were published in The Lancet Oncology in 2019. In 2018, Janssen Biotech, Inc. entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib.

About Non-Small Cell Lung Cancer
Worldwide, lung cancer is one of the most common cancers, and NSCLC makes up 80 to 85 percent of all lung cancers.13,14 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.15 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase supporting cell growth and division.16 EGFR mutations are present in 10 to 15 percent15,16,17,18,19 of people with NSCLC adenocarcinoma and occur in 40 to 50 percent of Asians.20,21 The five-year survival rate for all people with metastatic NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent.22,23

RYBREVANT IMPORTANT SAFETY INFORMATION 8 WARNINGS AND PRECAUTIONS
Infusion Related Reactions 8
RYBREVANT can cause infusion-related reactions (IRR); signs and symptoms of IRR include dyspnea, flushing, fever, chills, nausea, chest discomfort, hypotension, and vomiting.

Based on the safety population, IRR occurred in 66% of patients treated with RYBREVANT. Among patients receiving treatment on Week 1 Day 1, 65% experienced an IRR, while the incidence of IRR was 3.4% with the Day 2 infusion, 0.4% with the Week 2 infusion, and cumulatively 1.1% with subsequent infusions. Of the reported IRRs, 97% were Grade 1-2, 2.2% were Grade 3, and 0.4% were Grade 4. The median time to onset was 1 hour (range 0.1 to 18 hours) after start of infusion. The incidence of infusion modifications due to IRR was 62% and 1.3% of patients permanently discontinued RYBREVANT due to IRR.

Premedicate with antihistamines, antipyretics, and glucocorticoids and infuse RYBREVANT as recommended. Administer RYBREVANT via a peripheral line on Week 1 and Week 2. Monitor patients for any signs and symptoms of infusion reactions during RYBREVANT infusion in a setting where cardiopulmonary resuscitation medication and equipment are available. Interrupt infusion if IRR is suspected. Reduce the infusion rate or permanently discontinue RYBREVANT based on severity.

Interstitial Lung Disease/Pneumonitis 8
RYBREVANT can cause interstitial lung disease (ILD)/pneumonitis. Based on the safety population, ILD/pneumonitis occurred in 3.3% of patients treated with RYBREVANT, with 0.7% of patients experiencing Grade 3 ILD/pneumonitis. Three patients (1%) discontinued RYBREVANT due to ILD/pneumonitis.

Monitor patients for new or worsening symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold RYBREVANT in patients with suspected ILD/pneumonitis and permanently discontinue if ILD/pneumonitis is confirmed.

Dermatologic Adverse Reactions 8
RYBREVANT can cause rash (including dermatitis acneiform), pruritus and dry skin. Based on the safety population, rash occurred in 74% of patients treated with RYBREVANT, including Grade 3 rash in 3.3% of patients. The median time to onset of rash was 14 days (range: 1 to 276 days). Rash leading to dose reduction occurred in 5% of patients, and RYBREVANT was permanently discontinued due to rash in 0.7% of patients.

Toxic epidermal necrolysis occurred in one patient (0.3%) treated with RYBREVANT.

Instruct patients to limit sun exposure during and for 2 months after treatment with RYBREVANT. Advise patients to wear protective clothing and use broad-spectrum UVA/UVB sunscreen. Alcohol-free emollient cream is recommended for dry skin.

If skin reactions develop, start topical corticosteroids and topical and/or oral antibiotics. For Grade 3 reactions, add oral steroids and consider dermatologic consultation. Promptly refer patients presenting with severe rash, atypical appearance or distribution, or lack of improvement within 2 weeks to a dermatologist. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

Ocular Toxicity 8
RYBREVANT can cause ocular toxicity including keratitis, dry eye symptoms, conjunctival redness, blurred vision, visual impairment, ocular itching, and uveitis. Based on the safety population, keratitis occurred in 0.7% and uveitis occurred in 0.3% of patients treated with RYBREVANT. All events were Grade 1-2. Promptly refer patients presenting with eye symptoms to an ophthalmologist. Withhold, dose reduce or permanently discontinue RYBREVANT based on severity.

Embryo Fetal Toxicity 8
Based on its mechanism of action and findings from animal models, RYBREVANT can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment and for 3 months after the final dose of RYBREVANT.

Adverse Reactions 8
The most common adverse reactions (≥20%) were rash (84%), IRR (64%), paronychia (50%), musculoskeletal pain (47%), dyspnea (37%), nausea (36%), fatigue (33%), edema (27%), stomatitis (26%), cough (25%), constipation (23%), and vomiting (22%). The most common Grade 3 to 4 laboratory abnormalities (≥2%) were decreased lymphocytes (8%), decreased albumin (8%), decreased phosphate (8%), decreased potassium (6%), increased alkaline phosphatase (4.8%), increased glucose (4%), increased gamma-glutamyl transferase (4%), and decreased sodium (4%).