On December 3, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM; HKEX:13) reported that, following the 2021 negotiations with the China National Healthcare Security Administration ("NHSA"), on January 1, 2022 the updated National Reimbursement Drug List ("NRDL") will continue to include ELUNATE (fruquintinib) and will now include SULANDA (surufatinib) (Press release, Hutchison China MediTech, DEC 3, 2021, View Source [SID1234596427]).

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Christian Hogg, Chief Executive Officer of HUTCHMED, said, "We welcome the addition of SULANDA into the NRDL, along with the renewal of ELUNATE. The NRDL has made it possible for novel therapies to gain wide reach across the country for diseases with large patient populations."

ELUNATE was first included in the NRDL on January 1, 2020, for the treatment of metastatic colorectal cancer ("CRC"). CRC was the third most diagnosed form of cancer by incidence in China in 2020, with an estimated 450,000 to 550,000 new cases each year[1].

SULANDA was approved in China for the treatment of advanced non-pancreatic neuroendocrine tumors ("NETs") in December 2020 and for advanced pancreatic NETs in June 2021. In China, there were an estimated 71,300 newly diagnosed NET patients in 2020, with potentially up to 300,000 patients living with the disease.[2]

HUTCHMED’s third oncology drug, ORPATHYS (savolitinib), is the first and only approved MET inhibitor in China for the treatment of patients with non-small cell lung cancer ("NSCLC") with MET exon 14 skipping alterations. It was also included in the 2021 negotiations with the NHSA, however HUTCHMED and AstraZeneca, its partner on ORPATHYS, declined inclusion in the NRDL for 2022. This position will be reassessed next year ahead of the next NRDL update. In China, there are an estimated 13,000 newly diagnosed NSCLC patients with MET exon 14 skipping alterations each year.1

About the NRDL
In recent years, the government in China has placed great importance on improving the public affordability of drug use. The NHSA regularly convenes a broad network of experts in medicine, pharmacology and pharmaco­economics to identify innovative drugs to be considered for inclusion in the NRDL. This has led to expansion of reimbursement of Category B drugs, which increasingly include novel oncology drugs. Reimburse­ment of Category B drugs requires varying degrees of copayment from patients, depending on their province of residence or type of NHSA insurance scheme enrollment. Agreements for all included drugs are generally renewed every two years.

In this latest update of the NRDL, the NHSA is adding or renewing over 30 Category B oncology drugs, including ELUNATE and SULANDA. Effective January 1, 2022, included NRDL drugs are expected to be made available in all state-run hospital pharmacies in China and reimbursement will commence for patients included in NHSA insurance schemes.

About fruquintinib (ELUNATE in China)
Fruquintinib is a highly selective and potent oral inhibitor of vascular endothelial growth factor receptors ("VEGFRs") -1, -2 and -3. VEGFR inhibitors play a pivotal role in blocking tumor angiogenesis. Fruquintinib was designed to improve kinase selectivity to minimize off-target toxicities, improve tolerability and provide more consistent target coverage. The generally good tolerability in patients to date, along with fruquintinib’s low potential for drug-drug interaction based on preclinical assessment, suggests that it may also be highly suitable for combinations with other anti-cancer therapies.

Fruquintinib is marketed in China under the brand name ELUNATE for the treatment of metastatic CRC. It is currently under clinical development for the treatment of gastric cancer and metastatic breast cancer, and in combination with PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317, developed by BeiGene, Ltd.) and sintilimab (TYVYT in China, IBI308, developed by Innovent Biologics, Inc.). The U.S. Food and Drug Administration ("FDA") granted Fast Track Designation for the development of fruquintinib for treating metastatic CRC in June 2020. A Phase III registration study of fruquintinib in metastatic CRC, FRESCO-2, is currently underway in the U.S., Europe, Japan and Australia.

HUTCHMED retains all rights to fruquintinib outside of China. In China, HUTCHMED is partnered with Eli Lilly and Company. Since October 2021, HUTCHMED has been responsible for development and execution of all on-the-ground medical detailing, promotion and local and regional marketing.

About surufatinib (SULANDA in China)
Surufatinib is a novel, oral inhibitor that selectively inhibits the tyrosine kinase activity associated with VEGFR and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects.

Surufatinib is marketed in China under the brand name SULANDA for the treatment of patients with advanced NETs. It is currently under clinical development in combination with anti-PD-1 monoclonal antibodies, including with tislelizumab and toripalimab (TUOYI, developed by Shanghai Junshi Biosciences Co., Ltd.). A U.S. FDA New Drug Application (NDA) submission was accepted in June 2021, followed by a Marketing Authorisation Application (MAA) submission to the European Medicines Agency (EMA) validated in July 2021. In the U.S., surufatinib was granted Fast Track Designations for development in pancreatic and non-pancreatic NETs in April 2020, and Orphan Drug Designation for pancreatic NETs in November 2019.

HUTCHMED currently retains all rights to surufatinib worldwide.

About savolitinib (ORPATHYS in China)
Savolitinib is an oral, potent, and highly selective MET inhibitor that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

Savolitinib is marketed in China under the brand name ORPATHYS for the treatment of patients with NSCLC with MET exon 14 skipping alterations who have progressed following prior systemic therapy or are unable to receive chemotherapy. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers, as a single treatment and in combination with other medicines.

In 2011, following its discovery and initial development by HUTCHMED, AstraZeneca and HUTCHMED entered a global licensing agreement to jointly develop and commercialize savolitinib. Joint development in China is led by HUTCHMED, while AstraZeneca leads development outside of China. HUTCHMED is responsible for the marketing authorization, manufacturing and supply of savolitinib in China. AstraZeneca is responsible for the commercialization of savolitinib in China and worldwide. Sales of savolitinib are recognized by AstraZeneca.

On December 3, 2021 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported the publication of preclinical research of zunsemetinib in pancreatic cancer in the peer-reviewed journal Science Translational Medicine, on December 1, 2021 (Press release, Aclaris Therapeutics, DEC 3, 2021, View Source [SID1234596443]).

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The article, entitled "The MK2/Hsp27 axis is a major survival mechanism for pancreatic ductal adenocarcinoma under genotoxic stress," presents the results from a preclinical study using patient-derived cell lines and an autochthonous pancreatic ductal adenocarcinoma mouse model that evaluated the role of MK2, as well as the impact of zunsemetinib (ATI-450), Aclaris’ investigational oral MK2 inhibitor, in pancreatic cancer. This study was a multi-year collaboration between Aclaris and Washington University School of Medicine, led by the laboratory of Dr. Kian-Huat Lim, MD, PhD, Associate Professor in Oncology and Dr. Patrick Grierson, MD, PhD, Assistant Professor in Oncology.

In the study, Dr. Lim and his team identified the MK2/HSP27 axis as an important resistance mechanism resulting in pancreatic tumor cell survival following exposure to components of FOLFIRINOX chemotherapy – the current standard-of-care treatment for pancreatic cancer. His team also demonstrated that DNA damage induced by FOLFIRINOX chemotherapy components upregulated tumor necrosis factor alpha (TNFa) in pancreatic cancer cells, which had the dual effect of impacting cell death and cell survival, and that the selective inhibition of MK2 downstream of TNFa signaling abrogated survival through blocking HSP27 activation and beclin1 mediated autophagy, which allowed TNFa to execute its pro-death mechanism. With this understanding, his team then showed that mouse survival in an autochthonous KPPC model of pancreatic cancer was statistically significantly (p<0.001) extended when dosed with zunsemetinib in combination with FIRINOX (a murine version of FOLFIRINOX).

"This study introduces a new MK2-targeted approach for the treatment of pancreatic cancer," said Dr. Lim. "We are very excited about the potential of this therapeutic combination and believe it should be advanced into clinical trials to determine whether MK2 inhibition can strengthen the effect of mainstay FOLFIRINOX chemotherapy in patients with pancreatic cancer without incurring additional side effects."

Based on these results and clinical data generated from Aclaris’ clinical development program with zunsemetinib, Aclaris is considering a future clinical program for the treatment of patients with pancreatic cancer using one of Aclaris’ other MK2 inhibitor drug candidates.

The authors of the article are Patrick M. Grierson, Paarth B. Dodhiawala, Yi Cheng, Timothy Hung-Po Chen, Iftikhar Ali Khawar, Qing Wei, Daoxiang Zhang, Lin Li, John Herndon, Joseph B. Monahan, Marianna B. Ruzinova, and Kian-Huat Lim, and the article can be accessed here: View Source

On December 3, 2021 HOOKIPA Pharma Inc. (NASDAQ: HOOK, ‘HOOKIPA’), a company developing a new class of immunotherapeutics based on its proprietary arenavirus platform, reported that HOOKIPA’s management team will participate in virtual investor meetings and present at The JMP Securities Hematology and Oncology Summit that will be held December 6-7, 2021 (Press release, Hookipa Biotech, DEC 3, 2021, View Source [SID1234596444]).

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Corporate Presentation: Tuesday, December 7, 2021 at 1:20 PM EST

The webcast of the presentation will be available within the Investors & Media section of HOOKIPA’s website at View Source An archived replay will be accessible for 30 days following the event.

On December 3, 2021 Akari Therapeutics, Plc (Nasdaq: AKTX), a late-stage biopharmaceutical company focused on innovative therapeutics to treat orphan autoimmune and inflammatory diseases where complement (C5) and/or leukotriene (LTB4) systems are implicated, reported its financial results for the third quarter of 2021 and recent clinical progress (Press release, Akari Therapeutics, DEC 3, 2021, View Source [SID1234596634]).

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Akari’s two lead programs, in BP and pediatric HSCT-TMA, are in Phase III clinical development and both have been granted Orphan Drug and Fast Track designations by the U.S. Food and Drug Administration (FDA). The Company also has earlier stage programs addressing ophthalmology and pulmonary diseases.

"During 2021, Akari has been very active and focused on the launch of our two orphan Phase III programs for BP and HSCT-TMA as well as the further development of our lung and eye franchises based on new formulations of our lead asset, nomacopan," said Clive Richardson, Chief Executive Officer of Akari Therapeutics. "We now expect multiple readouts across our key ongoing and proposed programs over the next 12-18 months."

Clinical highlights

Phase III clinical trial in patients with bullous pemphigoid

BP is a severe autoimmune blistering disease of the elderly with no specific approved treatments.

The Company has opened the first sites for its Phase III study of nomacopan for the treatment of BP and anticipates commencing treatment by the end of 2021.
The FDA and the European Medicines Agency (EMA) have both granted Orphan Drug Designation for nomacopan for the treatment of BP, and the FDA has granted Fast Track designation to nomacopan in BP.
The Company is considering additional opportunities to expand into other dermatological conditions where both complement C5 activation and LTB4 are believed to have key roles in driving the disease pathology including hidradenitis suppurativa and other pemphigoid diseases.
Phase III clinical trial in patients with pediatric HSCT-TMA

HSCT-TMA is a severe disease in pediatric patients with an approximately 80% mortality rate in patients with proteinuria and elevated terminal complement activity. There are no approved treatments.

Phase III study in pediatric HSCT-TMA is now enrolling and treating patients.
The FDA has granted both Fast Track and Orphan Drug Designations for nomacopan for the treatment of pediatric HSCT-TMA.
Success in pediatric HSCT-TMA would provide opportunities to expand into adult HSCT-TMA and related TMA-like diseases where complement and LTB4 are believed to have important roles such as atypical hemolytic uremic syndrome, systemic lupus erythematosus and anti-phospholipid syndrome.
OTHER CLINICAL PROGRAMS

Akari Therapeutics is also pursuing other earlier stage programs that are primarily focused on large disease areas with high unmet need and where complement and leukotriene pathways are implicated. For these programs, the Company is using alternative formulations to the subcutaneous delivery of nomacopan including topical, nebulized or long-acting engineered forms, which provide an opportunity for separate partnering options.

Ophthalmology program

Recent publications (Eskandarpour et al 2020 and 2021) support a potential therapeutic role for longer acting PAS-nomacopan in sight-threatening retinal diseases given its inhibition of both complement and vascular endothelial growth factor (VEGF) via its inhibition of LTB4. This unique combination may be particularly relevant to geographic atrophy (GA)/dry AMD where complement is a key treatment target as evidenced by Phase II and III data from Apellis and Iveric Bio, and VEGF inhibition by nomacopan may prevent neo vascularisation, which has been seen in some GA patients treated with other complement inhibitors.
In order to increase the interval between intravitreal injections into the back of the eye, the program is being advanced with PAS-nomacopan, an engineered form of nomacopan with an extended half-life. Data from pharmacokinetics (PK) studies with PAS-nomacopan to estimate injection interval in the back of the eye are expected by the end of 2021.
Animal models described in a recent publication (1) highlight that nomacopan eye drops reduced inflammation more than both standard treatments, cyclosporin and the steroid dexamethasone in a model of allergic eye disease.
Eskandarpour 2021, Allergy: Allergic eye disease: blocking LTB4/C5 in vivo suppressed disease and Th2 & Th9 cells
Lung program

An observational study sponsored by Akari in COVID-pneumonia showed that elevated levels of C5a, C5b9 and LTB4 were present in COVID-pneumonia patients and that the levels of C5a (p = 0.001) and C5b9 (p=0.019), which are potential biomarkers for disease progression, rose significantly in patients that worsened. These findings align with a prior, separate Akari-sponsored observational study in chronic obstructive cardiopulmonary disease (COPD) patients that demonstrated that the level of C5a was significantly correlated with the severity of the exacerbations (p=0.01).
Akari is investigating the PK of inhaled nomacopan in the lung and a proof of principle study in exacerbating COPD patients to further evaluate the impact of inhibiting C5 and LTB4 with nomacopan.
The COVID-pneumonia observational findings are being further evaluated to explore the potential role of biomarkers in identifying the most appropriate COVID-pneumonia patients who might respond to nomacopan.
Trauma

The damaging role of both C5 and LTB4 has been implicated in trauma and Akari is exploring both blast injury and hemorrhagic shock with the United States Army Institute of Surgical Research (USAISR) where nomacopan has been shown to improve survival in pre-clinical studies. In addition, a separate new collaborative study in traumatic brain injury and subarachnoid hemorrhage in man is being initiated in the UK.
Histamine inhibitor

Votucalis, a molecule with a similar origin to nomacopan, has a unique mode of action by binding directly to histamine and preventing the activation of all four histamine G-protein coupled receptors. Ongoing work in collaboration with Durham and Newcastle Universities is focused on expanding the Company’s existing dermatology franchise with initial skin penetration data indicating a potential opportunity for topical delivery.
Third Quarter 2021 Financial Results

As of September 30, 2021, the Company had cash of approximately $13.4 million, compared to cash of approximately $14.1 million at December 31, 2020. In July 2021, Akari closed a private placement of approximately $12.3 million in gross proceeds by issuing approximately 7.9 million of the Company’s ADSs.
In September 2020, Akari entered into a securities purchase agreement with Aspire Capital Fund, LLC (Aspire Capital) whereby Aspire Capital is committed to purchase up to an aggregate of $30.0 million of the Company’s ADSs. During the nine months ended September 30, 2021, the Company sold to Aspire Capital ordinary shares for gross proceeds of $2.0 million. As of September 30, 2021, $22.0 million of the original purchase commitment remains available.
Research and development (R&D) income for the third quarter 2021 were approximately $0.4 million, as compared to approximately $1.6 million in the same quarter the prior year. This decrease in income was primarily due to lower R&D tax credit received for the 2020 tax year and higher expenses incurred for clinical trials in the third quarter 2021.
General and administrative expenses for the third quarter 2021 were approximately $1.9 million, as compared to approximately $1.8 million in the same quarter the prior year.
For the third quarter 2021, total other income was approximately $12,000 as compared to total other income of approximately $1.2 million in the third quarter of 2020. This change was primarily due to the accounting reclassification of warrant liabilities to shareholders’ equity as of December 2020.
Net loss for the third quarter 2021 was approximately $1.5 million, as compared to net income of approximately $0.9 million for the period of 2020. This decrease was primarily due to the aforementioned lower R&D income as well as lower total other income.

On December 3, 2021 Zai Lab Limited (NASDAQ: ZLAB; HKEX: 9688), a patient-focused, innovative, commercial-stage, global biopharmaceutical company, reported that the National Reimbursement Drug List (NRDL) released by China’s National Healthcare Security Administration (NHSA) has been updated to include ZEJULA (niraparib) as a first-line maintenance treatment of adult patients with advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (collectively termed as ovarian cancer) following a response to platinum-based chemotherapy, regardless of biomarker status (Press release, Zai Laboratory, DEC 3, 2021, View Source [SID1234596445]).

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"A key part of Zai Lab’s mission is to bring transformative medicines to patients in China," said Dr. Samantha Du, Founder, Chairperson, and Chief Executive Officer of Zai Lab. "The inclusion of ZEJULA in the NRDL for first-line maintenance treatment of ovarian cancer is an important step in achieving that mission. We are grateful for this action by the NHSA to make ZEJULA more accessible to Chinese patients with ovarian cancer."

"NHSA reimbursement will increase ZEJULA’s availability for many patients in need across China," said William Liang, Chief Commercial Offer. "It is the only PARP inhibitor approved as monotherapy for first-line and recurrent maintenance therapy for ovarian cancer patients regardless of biomarker status in China. This action underscores ZEJULA’s clinical value for a broad range of ovarian cancer patients."

In November 2021, Zai Lab announced that the Phase 3 PRIME study of ZEJULA as maintenance therapy met its primary endpoint and demonstrated a statistically significant and clinically meaningful progression-free survival (PFS) benefit with a manageable safety profile in Chinese patients with newly diagnosed advanced ovarian cancer following a response to platinum-based chemotherapy, regardless of biomarker status.

In December 2020, ZEJULA was included in the NRDL as a maintenance treatment of adult patients with platinum-sensitive, recurrent ovarian cancer.

About Ovarian Cancer

Ovarian cancer is one of the most common gynecologic cancers in China, with over 55,000 newly diagnosed cases and 37,000 deaths in China annually1. While platinum-based chemotherapy is effective at inducing an initial response in ovarian cancer, the disease will recur in the majority of women. New agents that prolong the duration of response following platinum-based treatment and delay the relapse of ovarian cancer will benefit patients with ovarian cancer in China.

Globocan 2020.

About ZEJULA (niraparib)

ZEJULA (niraparib) is an oral, once-daily poly (ADP-ribose) polymerase (PARP) inhibitor indicated as monotherapy for the maintenance treatment of adult patients with advanced and recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response (complete or partial) to first- and second-line platinum-based chemotherapy.

Zai Lab has completed several studies in Chinese patients with ovarian cancer:

In November 2021, Zai Lab announced positive topline results from the company’s Phase 3 PRIME study of ZEJULA as maintenance therapy for Chinese patients with first-line platinum-responsive, advanced ovarian cancer, regardless of biomarker status.

In September 2020, Zai Lab announced that ZEJULA demonstrated a significant PFS benefit with an improved safety profile in the company’s Phase 3 NORA study of ZEJULA as maintenance therapy for Chinese patients with platinum-sensitive, recurrent ovarian cancer, regardless of biomarker status.

A Phase 1 pharmacokinetic (PK) study of ZEJULA was conducted in Chinese patients with ovarian cancer.

ZEJULA is also being evaluated in China in a Phase 1b/2 study in combination with tebotelimab (PD-1 x LAG-3 DART molecule) for advanced gastric cancer, triple negative breast cancer, biliary tract cancer, and endometrial cancer.

Zai Lab has a collaboration and license agreement with GSK for the development and commercialization of ZEJULA in mainland China, Hong Kong, and Macau.