ALCMI and Biodesix Initiate Prospective Study to Predict Overall Survival Using Checkpoint Immunotherapy for Front-Line Lung Cancer in Patients with High PDL1 Expression

On August 31, 2020 Addario Lung Cancer Medical Institute (ALCMI) and Biodesix, Inc. reported they will begin an observational study to prospectively evaluate the clinical utility of biomarkers, including the proteomic Primary Immune Response (PIR) test, for front-line non-small cell lung cancer (NSCLC) patients receiving immunotherapy with and without the addition of systemic platinum-based chemotherapy who have high expression of program death ligand-1 (PD-L1) on their tumor cells (Press release, Biodesix, AUG 31, 2020, View Source [SID1234564154]).

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Biodesix is a leader in lung cancer diagnostic solutions, and has developed a serum-based proteomic test, Primary Immune Response (PIR) that, in retrospective studies, identified a pretreatment immune profile that predicts response to anti-PD-1 therapy.

ALCMI is a patient-founded not-for-profit global research consortium dedicated to catalyzing and accelerating the discovery, development, and delivery of new and more effective treatment options for lung cancer patients.

Together, they aim to enroll 390 treatment naïve advanced stage non-squamous NSCLC patients with ≥50 percent expression of PD-L1 at leading cancer institutions in the U.S.

"Immunotherapy has revolutionized our treatment of lung cancer patients. Many patients, especially those with high expression of the associated PD-L1 marker, prefer a nonchemotherapy treatment option. Clinical experience, however, suggests that this may not be the best therapy for all of these patients," said Mary Jo Fidler, MD, Rush University Medical Center.

Adding systemic chemotherapy (carboplatin and pemetrexed) to pembrolizumab, an FDAapproved triplet immunotherapy regimen (Langer Lancet Oncol. 2016) independent of PD-L1 status, may be a way to mitigate rapidly progressive disease in high PD-L1 expressers receiving pembrolizumab monotherapy. However, applying the triplet combination to all patients with PDL1 ≥50 percent may expose them to increased side effects and cost of therapy without additional benefit.

"ALCMI is dedicated to improving overall survival for all lung cancer patients in the most targeted way possible," said Tony Addario, ALCMI chair and CEO. "This study reflects that commitment and will drive the pursuit of new and better care options for patients with NSCLC."

"ALCMI is dedicated to improving overall survival for all lung cancer patients in the most targeted way possible," said Tony Addario, ALCMI chair and CEO. "This study reflects that commitment and will drive the pursuit of new and better care options for patients with NSCLC."

In a study presented at the European Society for Medical Oncology, the Biodesix PIR test demonstrated utility in retrospectively classifying second-line NSCLC patients treated with nivolumab by overall survival. The immunotherapy resistant subgroup in the test demonstrated activation in the complement, acute phase, extra-cellular matrix and wound healing pathways. The proteomic test classification is independent of PD-L1 status and uses mass spectrometry in combination with machine learning to analyze circulating proteins in blood.

"We know that immunotherapy by itself does not work for everyone," said Scott Hutton, CEO of Biodesix. "With the physical and financial toxicity associated with these therapies, a biomarker that can predict survival or early death would be critical in determining the best therapeutic regimen for lung cancer patients."

Hansa Biopharma announces participation in Fall conferences and an updated financial calendar

On August 30, 2020 Hansa Biopharma, the leader in immunomodulatory enzyme technology for rare IgG mediated diseases, reported that the Company’s management team will present at the following upcoming investor conferences in September (Press release, Hansa Biopharma, AUG 30, 2020, View Source [SID1234564159]):

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Pareto Securities Health Care Conference on Thursday September 3, 2020, at 15:30 CET
Citibank’s Annual BioPharma Virtual Conference on Wednesday September 9, 2020
H.C.Wainwrigth Healthcare Conference on Tuesday September 15, 2020
Bank of America Merill Lynch Healthcare Conference on Wednesday September 16, 2020
MorganStanley Global Healthcare Conference on Friday September 18, 2020 at 8:00am EST/14:00 CET
ABG Small & Midcap Seminar, Copenhagen on Wednesday September 23, 2020 at 13:30 CET
A link to the presentations and webcasts will be available on the Events & Presentations page of the Company’s website at View Source

Calendar

Aug 31,2020 Kempen Road Show, Tel Aviv/Paris/Benelux (virtual)
Sep 3, 2020 Pareto Healthcare Conference, Stockholm (virtual)
Sep 9, 2020 Citibank’s Annual BioPharma Virtual Conference, Boston (virtual)
Sep 15, 2020 H.C. Wainwright Healthcare Conference, NYC (virtual)
Sep 16, 2020 Bank of America Merill Lynch Healthcare Conf., London (virtual)
Sep 18, 2020 MorganStanley Global Healthcare Conference, NYC (virtual)
Sep 23, 2020 ABG Small & Mid Cap Seminar, Copenhagen and virtual
Oct 22, 2020 Interim Report Jan-Sep 2020
Oct 29, 2020 Hansa Biopharma Capital Markets Day, Copenhagen and virtual
Nov 17, 2020 Bryan Garnier Healthcare Conference, Paris
Nov 18, 2020 Jefferies Healthcare Conference, London
Nov 25, 2020 Ökonomisk Ugebrev Life Science Conference, Copenhagen
Feb 2, 2021 Interim report for Jan – Dec 2020
April 8, 2021 Annual Report 2020
April 22, 2021 Interim report for Jan – Mar 2021
July 15, 2021 Interim report for Jan – Jun 2021
Oct 21, 2021 Interim report for Jan – Sep 2021

GenScript Reports 2020 Interim Results and Provides Business Update

On August 30, 2020 GenScript Biotech Corp. (Stock Code: 1548.HK), a leading global biotechnology company, reported interim results for the six months ended June 30, 2020 and provided a corporate update (Press release, GenScript, AUG 30, 2020, View Source [SID1234564158]). Revenue of the Group for the six months ended June 30, 2020 was approximately US$166.4 million, representing an increase of 36.5% from the same period in 2019. The external revenue for non-cell therapy business was approximately US$143.3 million, representing an increase of 41.6% from the same period of 2019. The adjusted profit of non-cell therapy business more than doubled. The revenue for cell therapy business was approximately US$23.1 million, representing an increase of 11.6% from the same period of 2019.

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In the first half of 2020, the Group maintained strong momentum across all four business segments. Among others, life science CRO business delivered impressive results and saw fastest growth since IPO of the Company, with revenue increasing by 49.1%. Revenue from CDMO business (GenScript ProBio) increased by over 100% in the first half of 2020. Despite the COVID-19 outbreak, industrial synthetic biology business managed to grow faster than the industry average. In the cell therapy segment, the subsidiary Legend Biotech was listed on Nasdaq Global Market in June 2020 as China’s first CAR-T stock, expecting to initiate a biologics license application (BLA) for its first CAR-T therapy ciltacabtagene autoleucel (cilta-cel) with US Food and Drug Administration (FDA) by the end of 2020.

"GenScript’s business is well on the right track of increasing revenue and profit. We have confidence in continued future growth," said Dr. Frank Zhang, Founder & Chairman of GenScript, "I believe that, under the leadership of rotating CEO Dr. Liu Zhenyu, the Company will maintain strong momentum and achieve brilliant success."

Non-cell therapy business delivered impressive results, witnessing fastest growth since IPO of GenScript

For the six months ended June 30, 2020, the external revenue for non-cell therapy business was approximately US$143.3 million, representing an increase of 41.6% as compared with approximately US$101.2 million for the same period of 2019. The gross profit of non-cell therapy business was approximately US$95.4 million, representing an increase of 48.8% as compared with approximately US$64.1 million for the same period of 2019. The adjusted net profit of non-cell therapy business was approximately US$25.2 million, representing an increase of 110.0% as compared with approximately US$12.0 million for the same period of 2019.

In terms of results of the four business segments, revenue from life science services and products amounted to approximately US$115.0 million, representing an increase of 39.9% from the same period in 2019. The gross profit was approximately US$78.0 million, representing an increase of 49.1% from the same period in 2019. The gross profit margin increased from 63.6% for the same period last year to 67.8% this year. The adjusted operating profit of life science services and products (excluding share-based compensation expenses and central management expenses) was approximately US$41.6 million, representing an increase of 65.8%. Revenue growth was mainly attributable to the (i) successful commercial operation that focused on COVID-19 related products such as protein and antibody, (ii) expanded capacity and productivity in gene synthesis and customized reagent services, (iii) successful development of key accounts, and (iv) improvement of online commercial platform and tools to attract new customers.

Revenue from biologics CDMO business amounted to approximately US$19.0 million, representing an increase of 102.1%. The gross profit was approximately US$4.7 million, representing an increase of 51.6% as compared with approximately US$3.1 million for the same period in 2019. The adjusted operating loss from biologics development services narrowed. The rapid growth in revenue was mainly attributable to the (i) establishment of Good Manufacturing Practice ("GMP") capacity in both antibody development and plasmid and virus process, (ii) successful commercial operation in both the China and Asia-Pacific market, (iii) fast growing talent pool and introduction of senior management teams for sales and marketing teams, and (iv) enhancement of the capability and process to support the successful delivery of the ongoing projects. The operating loss was primarily attributable to the (i) lower gross profit due to significant fixed cost such as quality system and talent pool, etc. at early stage of business set up period, and (ii) significant investment in commercial and senior management team.

External revenue from industrial synthetic biology products increased by 2.9% from the same period in 2019. After adjusting for the effect of currency translation, the revenue grew 14%. The growth of the revenue was mainly attributable to the (i) continuous strategic implementation of key accounts business development and significant breakthroughs in both overseas and domestic feed enzymes markets and grain processing business in China, providing customized service to strategic accounts in strain development, process development and new enzymes products development, and (ii) further optimization of the organization structure and significant improvement of business capability of commercial team. The gross profit was approximately US$4.3 million, representing an increase of 16.2% from the same period in 2019. Gross profit margin increased from 30.3% for the same period last year to 38.4% this year. During the Reporting Period, the adjusted operating loss of industrial synthetic biology products narrowed to US$0.7 million.

Revenue of cell therapy increased by 11.6% to approximately US$23.1 million. The gross profit was approximately US$23.1 million. The adjusted operating loss of cell therapy was approximately US$96.4 million.

In the first half of 2020, GenScript captured a number of growth opportunities. As the world’s largest gene synthesis provider, GenScript’s life science CRO business witnessed fastest growth since IPO of GenScript in 2015, maintained its industry leadership, and continuously generated profit for the Group. Amid the COVID-19 outbreak, in response to intensified demand from downstream customers for detection and diagnostic raw materials, life science CRO business team provided first-class products and services for gene synthesis, protein synthesis, antibody preparation, and COVID-19 R&D and diagnosis, and teamed up with the industry to fight against COVID-19. In addition, GenScript, Duke-NUS Medical School (Duke-NUS), and the Diagnostics Development Hub (DxD) at Singapore’s Agency for Science, Technology and Research (A*STAR) launched cPass sVNT kit, a first-in-the-world rapid test kit of SARS-CoV-2 Surrogate Virus neutralizing antibodies. This is an example of GenScript’s ability to work together with global academia and quickly commercialize research results.

With its GMP plasmid production, GenScript’s CDMO team has assisted a number of companies at home and abroad in developing mRNA vaccines, including the first mRNA vaccine that obtained IND approval from China’s National Medical Products Administration (NMPA). CDMO team is also supporting 6 drug discovery and development programs related to COVID-19. The biologics CDMO platform served customers in the fight against the epidemic.

Cell therapy was granted China’s first "breakthrough therapy designation"; "China’s first CAR-T stock" was listed on the Nasdaq

In June 2020, Legend Biotech, a subsidiary of GenScript, was listed on the Nasdaq global select market, making it "China’s first CAR-T stock". Legend Biotech raised about US $500 million in the IPO, which is the largest IPO in the biotech industry so far this year.

In terms of clinical development, Legend Biotech has continuously advanced its first CAR-T product. At the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) meeting in May 2020, Legend Biotech presented updated results from Phase 1b/2 CARTITUDE-1 study of cilta-cel (LCARB38M/JNJ-4528) in the treatment of patients with relapsed or refractory multiple myeloma. At a median follow-up time of 11.5 months, the overall response rate (ORR) was maintained at 100%, and 86% of patients achieved stringent complete response. Legend Biotech has started enrolling patients who have received 1-3 lines of prior treatment and are refractory to lenalidomide for phase III global randomized study.

In August 2020, Legend Biotech was granted China’s first "breakthrough therapy designation", which is meant to speed up the approval of cilta-cel. In the first half of 2020, this product was granted orphan drug designation in South Korea and Japan. Earlier in 2019, this product obtained PRIME designation from European Medicines Agency (EMA) and orphan drug designation and breakthrough therapy designation from FDA. Legend Biotech expects its partner Jassen to initiate a BLA filing in US by the end of 2020. Janssen also intends to file a Marketing Authorization Application (MAA) with EMA in early 2021 and file BLAs in China and Japan in 2021.

Continued investment in core competencies bolsters GenScript’s solid progress

In the first half of 2020, GenScript’s four business segments progressed steadily under the established strategy. GenScript continuously invested in talent pipelines, innovation, R&D, infrastructure and other core competencies that are essential to the longevity of an enterprise, building underlying strength and bolstering GenScript’s solid progress.

For the six months ended June 30, 2020, the Group’s R&D expense was approximately US$115.5 million, representing an increase of 83.9% from the same period in 2019, in which the total investment in R&D was approximately US$101.6 million on cell therapy. The R&D expense of non-cell therapy business segments remained at about 10% of revenue. Continued R&D investment will underpin GenScript’s presence in the fast-growing market and help leverage GenScript’s leadership in gene synthesis to increase market penetration of other products and services.

In June 2020, GenScript started the molecular building (covering more than 20,000 m2) project in Zhenjing,Jiangsu Province for the innovative biologics R&D and production service platform. The molecular building is an important presence of GenScript in precision treatment and an important part of GenScript’s CRO/CDMO platform. After commissioning, the platform will become the world’s largest production and R&D platform for customized peptide services and China’s first one-stop service platform from neoantigen peptide R&D to GMP production, and will help GenScript maintain its competitive edge in peptide drugs and oligo services.

As development and approval of biologics and GCT drugs are thriving, GenScript will continue to invest in these areas to meet customer demand and propel future growth. At present, GenScript is building the second GMP plasmid plant in Zhenjiang, which will double the plasmid and virus capacity after completion. The third GMP plant designed for clinical and commercialization stages of GCT projects will be launched in the next few years. In terms of antibody drug development, GenScript is also building a GMP biologics facility in Nanjing to increase total capacity to 2,600 L.

The Group invested significantly in the cell therapy segment. In the first half of 2020, the R&D expense of cell therapy increased by 88.5% from the same period in 2019. In addition to clinical trial expenses for the BCMA program in US and China, Legend Biotech continues to invest in the next-generation cell therapy pipeline. The ongoing trials are targeting hematological tumors, solid tumors and infectious diseases, using autologous and allogeneic CAR-T technology. This will create new growth potential for Legend Biotech and help grow the business to become the world’s leading cell therapy company.

"Over the past 18 years, GenScript has come a long way to get on the fast track, building a strong foundation for breakthroughs. In the future, GenScript will continue to invest in enhancing core competencies. While establishing our presence in major global markets, we will stay committed to our four business segments, helping the Company get bigger and stronger," said Dr. Liu Zhenyu, Rotating CEO of GenScript.

CStone Receives US FDA IND Clearance for CS1001-201 Study to Evaluate Anti-PD-L1 Monoclonal Antibody Sugemalimab Monotherapy in R/R ENKTL

On August 30, 2020 CStone Pharmaceuticals (SUZHOU) Co., Ltd. ("CStone", HKEX: 2616) reported that the US Food and Drug Administration (FDA) has completed their review of the Investigational New Drug (IND) application for anti-PD-L1 monoclonal antibody sugemalimab (CS1001) monotherapy in the relapsed or refractory extranodal natural killer (NK)/T-cell lymphoma (R/R ENKTL) with study may proceed (SMP) letter received (Press release, CStone Pharmaceauticals, AUG 30, 2020, View Source [SID1234564157]).

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Sugemalimab is an investigational fully human, full-length anti-PD-L1 monoclonal antibody developed by CStone. Compared with other drugs of the same class, sugemalimab has a lower risk of immunogenicity and potential toxicities in patients. CS1001-201 is a single-arm, multicenter pivotal Phase II clinical study designed to evaluate sugemalimab monotherapy in R/R ENKTL. The IND clearance indicates that the ongoing CS1001-201 study in China will be extended to the US.

ENKTL is a subtype of mature T cell and NK cell lymphoma. Epidemiology of the disease is characterized by higher incidence rates in Asia than in Europe or North America. In China, ENKTL accounts for approximately 6% of all lymphoma cases[1]. R/R ENKTL is highly malignant and aggressive, and has a poor prognosis. Patients with R/R ENKTL lack effective salvage treatments if standard L-asparaginase-based regimens fail, and do not respond well to traditional treatments. For these patients, clinicians almost run out of treatment choices because the disease progresses rapidly with an extremely short overall survival (OS) as indicated by historically reported 1-year OS rate <20%[2]. The currently approved targeted monotherapy in China has a complete response (CR) rate of approximately 6%[3],[4]. There are vast unmet medical needs in this patient population of which the first-line treatment has failed. Sugemalimab is expected to provide new treatment options for these patients.

Dr. Jason Yang, Chief Medical Officer of CStone, commented: "For the treatment of ENKTL, CR rate is a critical outcome measure. Data reported for CS1001-201 study on 2019 ASH (Free ASH Whitepaper) meeting shows that sugemalimab demonstrated a CR rate of 33.3% with a durable response, an objective response rate (ORR) of 43.3%, and 1-year OS rate of 72.4%. These results represent a major breakthrough compared to current treatment options and support sugemalimab as a potential conditioning regimen for hematopoietic stem cell transplantation. We will work closely with the US FDA and the National Medical Products Administration (NMPA), to bring sugemalimab to R/R ENKTL patients worldwide soon."

Overview of the CS1001-201 trial

CS1001-201 is a single-arm, multicenter Phase II clinical study designed to evaluate sugemalimab monotherapy in R/R ENKTL. The primary endpoint of the trial is ORR assessed by an independent radiological review committee.

According to updated results reported at the 2019 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, as of October 8, 2019, a total of 32 patients with R/R ENKTL were enrolled in the study. All patients received sugemalimab 1200 mg intravenously every 3 weeks until disease progression or intolerable toxicity. The median duration of follow-up was 6.54 months (range, 0.72–15.64).

Preliminary efficacy data

Sugemalimab demonstrated robust efficacy with a high CR rate and durable response in R/R ENKTL patients:

Among the 30 efficacy-evaluable patients, the investigator-assessed ORR was 43.3%
10 patients (33.3%) achieved CR and were still in remission
3 patients (10.0%) achieved partial response (PR), and 1 additional patient achieved PR after pseudo-progression
The median duration of response (DoR) was not reached, and the maximum DoR was 10.9+ months
The 1-year OS was 72.4% (95% CI: 52.0%–85.2%)
Safety data

Sugemalimab was well tolerated in patients with R/R ENKTL:

30 patients (93.8%) reported treatment-emergent adverse events (TEAEs), 24 patients (75.0%) reported treatment-related adverse event (TRAEs), of which 3 (9.4%) had Grade >3 TRAEs
Grade 5 AEs were reported in 3 patients (9.4%), and none were assessed as related to sugemalimab
Immune-related AEs (irAEs) were reported in 5 patients (15.6%); except for one case of Grade 3 rash, all irAEs were Grade 1 in severity
TEAEs that led to permanent treatment discontinuation occurred in 4 patients (12.5%)
No deaths due to AEs were assessed as related to sugemalimab
About Sugemalimab

Sugemalimab is an investigational anti-PD-L1 monoclonal antibody discovered by CStone. Authorized by the U.S.-based Ligand Corporation, sugemalimab is developed by the OmniRat transgenic animal platform, which can generate fully human antibodies in one stop. As a fully human, full-length anti-PD-L1 monoclonal antibody, sugemalimab mirrors the natural G-type immunoglobulin 4 (IgG4) human antibody, which can reduce the risk of immunogenicity and potential toxicities in patients, a unique advantage over similar drugs.

Sugemalimab has completed a Phase I dose-escalation study in China. During Phase 1a and 1b stages of the study, sugemalimab showed good antitumor activity and good tolerability in multiple tumor types.

Currently, sugemalimab is being investigated in a number of ongoing clinical trials. In addition to a Phase I bridging study in the U.S., the clinical program in China includes one multi-arm Phase Ib study for several tumor types, one Phase II registrational study for lymphoma, and four Phase III registrational studies, respectively, for stage III/IV NSCLC, gastric cancer, and esophageal cancer.

FDA grants Priority Review of melflufen for patients with triple-class refractory multiple myeloma

On August 29, 2020 Oncopeptides AB (publ) (Nasdaq Stockholm: ONCO) reported that the US Food and Drug Administration, FDA, has granted priority review for Oncopeptides´ New Drug Application seeking approval of melflufen (INN melphalan flufenamide), in combination with dexamethasone for the treatment of adult patients with multiple myeloma whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent and one anti-CD-38 monoclonal antibody, (i.e., triple-class refractory multiple myeloma patients) (Press release, Oncopeptides, AUG 29, 2020, View Source [SID1234564153]). The FDA has set a PDUFA-date (Prescription Drug User Fee Act), which is the target date for their review of the New Drug Application, to February 28, 2021.

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The submission is based on the results from the pivotal phase 2 study HORIZON, evaluating intravenous melflufen in combination with dexamethasone in patients with relapsed refractory multiple myeloma, (RRMM).

"This is very exciting news. It is an important milestone for Oncopeptides, and a major step in making melflufen available for patients with multiple myeloma, who desperately need new treatment options", says Marty J Duvall, CEO of Oncopeptides AB. "I am looking forward to a continuing dialogue with the FDA while we make the product available to RRMM patients in the US through an expanded access program, in an FDA approved trial called sEAPort."

A Priority Review designation means that FDA’s goal is to take action on an application within 6 months (compared to 10 months under standard review). They will direct overall resources to the evaluation of applications for drugs that, "if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications".

About melflufen
Melflufen (INN melphalan flufenamide) is a first in class peptide-drug conjugate (PDC) that targets aminopeptidases and rapidly releases alkylating agents into tumor cells. Melflufen is rapidly taken up by myeloma cells due to its high lipophilicity and is immediately hydrolyzed by peptidases to release an entrapped hydrophilic alkylator payload. Aminopeptidases are overexpressed in tumor cells and are even more pronounced in advanced cancers and tumors with a high mutational burden. In vitro, melflufen is 50-fold more potent in myeloma cells than the alkylator payload itself due to the increased intracellular alkylator concentration. Melflufen displays cytotoxic activity against myeloma cell lines resistant to other treatments, including alkylators, and has also demonstrated inhibition of DNA repair induction and angiogenesis in preclinical studies. In the pivotal phase 2 HORIZON study melflufen plus dexamethasone demonstrated encouraging efficacy and a clinically manageable safety profile in heavily pretreated patients with relapsed refractory multiple myeloma, with primarily hematologic Adverse Events (AE) and a low incidence of non-hematologic AEs.