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HUTCHMED Announces NMPA Approval of Surufatinib (Sulanda® in China) for Advanced Pancreatic Neuroendocrine Tumors

On June 21, 2021 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM: HCM) repported that surufatinib has been granted approval for drug registration by the National Medical Products Administration of China ("NMPA") for the treatment of advanced pancreatic neuroendocrine tumors ("pNETs") (Press release, Hutchison China MediTech, JUN 21, 2021, View Source [SID1234584187]). This follows the approval of surufatinib in China in December 2020 for the treatment of advanced extra-pancreatic (non-pancreatic) neuroendocrine tumors ("epNETs").

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The Company was made aware through the website of the NMPA that surufatinib’s approval for drug registration by the NMPA for the treatment of pNETs was completed and is now pending certification.

Christian Hogg, Chief Executive Officer of HUTCHMED, commented, "Since its launch in January this year, patients with epNETs have benefited from treatment with surufatinib through its unique mode of action by both inhibiting angiogenesis and promoting the body’s immune response against tumor cells. With today’s approval, we are now able to provide this unique therapy to NET patients with pancreatic tumor origin as well."

Surufatinib is marketed in China under the brand name Sulanda.

HUTCHMED’s oncology commercial team today covers more than 2,500 hospitals across China. The team is led by a leadership team highly experienced in oncology products commercialization in China with deep knowhow in the field of NETs.

This NMPA approval was supported by the SANET-p study, a Phase III pivotal study (clinicaltrials.gov identifier: NCT02589821) in patients with advanced pancreatic NETs conducted in China. The study met the pre-defined primary endpoint of progression-free survival ("PFS") at a preplanned interim analysis and was stopped early. The positive results of this trial were highlighted in an oral presentation at the 2020 ESMO (Free ESMO Whitepaper) Congress and published in The Lancet Oncology1 in September 2020. Median PFS was 10.9 months for patients treated with surufatinib, as compared to 3.7 months for patients in the placebo group (hazard ratio ["HR"] 0.491; 95% confidence interval ["CI"] 0.391-0.755; p=0.0011). Benefit was observed across most major subgroups of pNET patients. The safety profile of surufatinib was manageable and consistent with observations in prior studies. Treatment was well tolerated for most patients, with discontinuation rates as a result of treatment emergent adverse events of 10.6% in the surufatinib group as compared to 6.8% in the placebo group.

In China, there were an estimated 71,300 newly diagnosed NET patients in 2020. Considering the current incidence to prevalence ratio, there may be as many as 300,000 patients living with the disease.2

About NETsNETs form in cells that interact with the nervous system or in glands that produce hormones. They can originate in various parts of the body, most often in the gut or the lungs and can be benign or malignant. NETs are typically classified as pNET or epNET. Approved targeted therapies include Sutent (for pNET only) and Afinitor for pNET and well-differentiated, non-functional gastrointestinal or lung NET.

According to Frost and Sullivan, there were 19,700 newly diagnosed cases of NETs in the U.S. in 2020. Importantly, NETs are associated with a relatively long duration of survival compared to other tumors.

About Surufatinib (Sulanda in China)

Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptor (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.

HUTCHMED currently retains all rights to surufatinib worldwide.

About Other Surufatinib Development

NETs in the U.S. and Europe: In the U.S., surufatinib was granted Fast Track Designations for development in pNET and epNET in April 2020, and Orphan Drug Designation for pNET in November 2019. A U.S. FDA NDA was submitted on April 30, 2021, and a MAA submission to the European Medicines Agency (EMA) is planned. The basis to support these filings includes the completed SANET-ep and SANET-p studies, along with existing data from surufatinib in U.S. epNET and pNET patients (clinicaltrials.gov identifier: NCT02549937).

epNETs in China: On December 30, 2020, surufatinib was granted drug registration approval by the NMPA for the treatment of epNET. Surufatinib is marketed in China under the brand name Sulanda. The approval was based on results from the SANET-ep study, a Phase III trial (clinicaltrials.gov identifier: NCT02588170) in patients with advanced epNETs conducted in China. The study met the pre-defined primary endpoint of PFS at a preplanned interim analysis. The positive results of this trial were highlighted in an oral presentation at the 2019 ESMO (Free ESMO Whitepaper) Congress and published in The Lancet Oncology in September 2020.3 Median PFS was significantly longer for patients treated with surufatinib at 9.2 months, compared to 3.8 months for patients in the placebo group (HR 0.334; 95% CI: 0.223-0.499; p<0.0001). Surufatinib had an acceptable safety profile, with the most common treatment-related adverse events of grade 3 or worse being hypertension (36% of surufatinib patients vs. 13% of placebo patients), proteinuria (19% vs. 0%) and anemia (5% vs. 3%).

Biliary tract cancer in China: In March 2019, HUTCHMED initiated a Phase IIb/III study comparing surufatinib with capecitabine in patients with advanced biliary tract cancer whose disease progressed on first-line chemotherapy. The primary endpoint is overall survival (OS) (clinicaltrials.gov identifier: NCT03873532).

Immunotherapy combinations: HUTCHMED entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies, including with tislelizumab (BGB-A317), Tuoyi (toripalimab) and Tyvyt (sintilimab), which are approved as monotherapies in China.

Transactions in connection with share buy-back program

On June 21, 2021 Genmab reported the initiation of a share buy-back program to mitigate dilution from warrant exercises and to honor our commitments under our Restricted Stock Units program (Press release, Genmab, JUN 21, 2021, View Source [SID1234584186]).

The share buy-back program is expected to be completed no later than June 30, 2021 and comprises up to 200,000 shares.

The following transactions were executed under the program from June 14, 2021, to June 18, 2021:

No. of shares

Average price (DKK)

Total value (DKK)

Accumulated through last announcement

Details of each transaction are included as an appendix to this announcement.

Following these transactions, Genmab holds 281,006 shares as treasury shares, corresponding to 0.43% of the total share capital and voting rights.

The share buy-back program is undertaken in accordance with Regulation (EU) No. 596/2014 (‘MAR’) and the Commission Delegated Regulation (EU) 2016/1052, also referred to as the "Safe Harbour Regulation." Further details on the terms of the share buy-back program can be found in our company announcement no. 11 dated February 23, 2021.

CytomX Therapeutics Announces Publication of First-in-Human Data for CX-2029 in Clinical Cancer Research

On June 21, 2021 CytomX Therapeutics, Inc. (Nasdaq: CTMX), a clinical-stage oncology-focused biopharmaceutical company pioneering a novel class of investigational conditionally activated therapeutics based on its Probody technology platform, reported that results from its Phase 1 first-in-human study of CX-2029 in patients with advanced solid tumors were published online in the peer-reviewed journal Clinical Cancer Research (Press release, CytomX Therapeutics, JUN 21, 2021, View Source [SID1234584185]). This study showed that CX-2029, currently being co-developed by CytomX and AbbVie, was generally well-tolerated and can elicit anti-tumor responses in certain patients.

"These results highlight that our industry-leading Probody platform can be successfully leveraged to create conditionally activated ADCs against previously undruggable targets. For the first time, CD71 has been shown to be a viable therapeutic cancer target," said Alison L. Hannah, M.D., senior vice president and chief medical officer of CytomX Therapeutics.

CD71 is a cell surface protein essential for iron uptake in dividing cells and is highly expressed in a number of solid and hematologic cancers. However, given its central role in iron metabolism, CD71 is present on most healthy cells and has been, until now, undruggable with conventional ADCs. CX-2029 is designed to be activated in the tumor microenvironment by tumor-associated proteases, thereby limiting off-tumor toxicity and creating a therapeutic window for CD71.

The goal of this Phase 1 dose-escalation, multicenter study was to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of CX-2029. A total of 45 patients were enrolled to receive CX-2029 intravenously every three weeks at dose levels ranging from 0.1 mg/kg to 5 mg/kg.

Encouraging preliminary clinical activity was observed at doses of 2 mg/kg and higher. Notably, three of four patients with squamous non-small cell lung carcinoma (NSCLC) had stable disease (SD) or better, including two confirmed partial responses (PRs) (at doses of 3 and 5 mg/kg); and seven of eight patients with head and neck squamous cell carcinoma (HNSCC) had SD or better, including one confirmed PR at 3 mg/kg and one prolonged SD ongoing at approximately 25 weeks, as of the reported August 2020 data cutoff.

Despite having received a median of three prior lines of cancer regimens (range, 1–16), these heavily-pretreated patients generally tolerated CX-2029 well. The most common dose-dependent adverse events were anemia and neutropenia, toxicities commonly associated with the payload of this ADC (monomethyl auristatin E). Based on several safety parameters, including no cycle 1 DLTs, no discontinuations due to toxicity, and a long-term tolerability that appeared to be acceptable for chronic administration with supportive care for anemia, 3 mg/kg every 3 weeks was declared the recommended Phase 2 dose.

The ongoing Phase 2 expansion study is evaluating CX-2029 as monotherapy in four cohorts: squamous NSCLC, HNSCC, esophageal and gastroesophageal junction cancers (both adenocarcinoma and squamous histologies), and diffuse large B-cell lymphoma. Initial results are expected in the fourth quarter of 2021.

Celsion Corporation Enters into $10 Million Strategic Loan Facility with Silicon Valley Bank

On June 21, 2021 Celsion Corporation (NASDAQ: CLSN), a clinical-stage company focused on DNA-based immunotherapy and next-generation vaccines, reported it has entered into a $10 million loan facility with Silicon Valley Bank (SVB) (Press release, Celsion, JUN 21, 2021, View Source [SID1234584184]). Celsion immediately used $6 million from this facility to retire all outstanding indebtedness with Horizon Technology Finance Corporation. The remaining $4 million will be available to be drawn down up to 12 months after closing and will be used for working capital and to fund the advancement of the Company’s product pipeline, including GEN-1 for the treatment of newly diagnosed advanced ovarian cancer, as well as other strategic initiatives intended to broaden its product pipeline.

"This loan facility provides us with financial and operating flexibility at very favorable terms, strengthens our balance sheet with the elimination of the Horizon debt and allows us to meet several key, value-driving milestones with our product-development initiatives," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "Including the $4 million that will become available to us in a year, we will have sufficient cash to fund current and planned operations into early 2025. We appreciate the support of SVB and their confidence in Celsion and the management team."

Tom Gordon, Managing Director of Life Science and Healthcare at Silicon Valley Bank, said, "We are pleased Celsion has selected SVB as its financial partner for this $10 million loan facility. We have confidence in the Company’s business strategy and look forward to Celsion reaching critical milestones including with GEN-1 for ovarian cancer and other strategic initiatives to broaden its product pipeline."

The funding is in the form of money market secured indebtedness bearing interest at a calculated WSJ Prime-based variable rate (currently 3.25%). Payments under the loan agreement are interest only for the first 24 months after loan closing, followed by a 24-month amortization period of principal and interest through the scheduled maturity date.

C4 Therapeutics Presents Pre-clinical Data on CFT7455, a Novel IKZF1/3 Degrader for the Treatment of Hematologic Malignancies, at the 16th Annual International Conference on Malignant Lymphoma

On June 21, 2021 C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company pioneering a new class of small-molecule medicines that selectively destroy disease-causing proteins through degradation, reported that pre-clinical data for CFT7455, the Company’s lead program. CFT7455 is an orally bioavailable MonoDAC targeting IKZF1/3 for the treatment of multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHL), including peripheral T-cell lymphoma (PTCL) and mantle cell lymphoma (MCL) (Press release, C4 Therapeutics, JUN 21, 2021, View Source [SID1234584183]). These results, which support clinical evaluation of CFT7455 in non-Hodgkin’s lymphomas, were delivered as a poster presentation at the 16th Annual International Conference on Malignant Lymphoma (ICML).

"We are pleased to share these pre-clinical data, which further validate the potential of our lead candidate, CFT7455, to generate deep and durable antitumor responses in non-Hodgkin’s lymphomas. IKZF1/3 proteins are essential transcription factors for B cell malignancies, including non-Hodgkin’s lymphomas, and we believe there is a compelling opportunity to explore the potential of optimized IKZF1/3 degradation as a much-needed therapeutic alternative," said Adam Crystal, M.D., Ph.D., chief medical officer of C4 Therapeutics. "These results, which are consistent with recent pre-clinical data in multiple myeloma presented at the AACR (Free AACR Whitepaper) Annual Meeting 2021, reinforce our belief that CFT7455 will provide significant clinical value in the treatment of hematologic malignancies as we advance the Phase 1/2 trial and prepare to share data in 2022."

Summary of Results

C4T conducted in vitro studies which demonstrated that CFT7455 binds to cereblon with high affinity, inducing potent and deep degradation of IKZF1 in pre-clinical NHL models. Notable observations include:

Cellular competition studies confirmed the high potency of CFT7455 as a cereblon binder (IC50 = 0.4 nM).
Treatment of the KiJK cell line of anaplastic large cell lymphoma (ALCL) with CFT7455 for 6 hours led to an 89% reduction in IKZF1 protein levels.
CFT7455 demonstrated potent antiproliferative activity across a panel of NHL cell lines with MYC, BCL2, and/or BCL6 translocations or rearrangements. This includes in vitro models of cutaneous T-cell lymphoma (CTCL), anaplastic large cell lymphoma (ALCL), mantle cell lymphoma (MCL), and high-grade B-cell lymphoma.
In xenograft models of NHL, CFT7455 achieved improved in vivo potency and efficacy, including deeper and more durable tumor regressions in models of ALCL, diffuse large B-cell lymphoma (DLBCL) and MCL, when compared to approved and investigational IMiD therapies. Notable observations include:

CFT7455 treatment (100 µg/kg/day, PO) led to durable tumor regression associated with deep IKZF1 degradation and IRF4 downregulation (7% and 25% remaining, respectively) in KiJK xenografts, where pomalidomide treatment was ineffective at a clinically relevant dose (3000 µg/kg/day).
In the TMD8 DLBCL xenograft model, which proved insensitive to IMiD treatment, CFT7455 (100 µg/kg) promoted tumor regression.
In the REC1 MCL xenograft model, doses of CFT7455 ≥ 10 µg/kg promoted tumor regression. Pharmacodynamic studies showed that CFT7455 (30 µg/kg) promoted degradation of IKZF1 and downregulation of cyclin D1 and E2F1.
CFT7455 achieved dose-dependent efficacy in both ALK- (DL-40) and ALK+ (KiJK) xenograft models, from 3-100 µg/kg with regressions at doses ≥ 30 µg/kg. In addition, CFT7455 was shown to be between >30-100 times more potent than other IKZF1/3 degraders in development.
Global proteomic studies showed only IKZF1/3 proteins were significantly degraded in DL-40 tumors with treatment of CFT7455, resulting in modulation of IFN-regulated genes.
These results support continued development of CFT7455, which C4T is currently exploring for the treatment of relapsed or refractory multiple myeloma and non-Hodgkin’s lymphomas following the initiation of a Phase 1/2 clinical study in June 2021.

C4T’s ICML poster presentation will be archived on the "Scientific Publications" page in the Investors section of the Company’s website, located at www.c4therapeutics.com.

About CFT7455
CFT7455 is an orally bioavailable MonoDAC (Monofunctional Degradation Activating Compound) designed to bind with high affinity to the E3 ligase adapter protein, cereblon, to target and degrade IKZF1/3 for the treatment of multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHLs), including peripheral T cell lymphoma (PTCL) and mantle cell lymphoma (MCL). In preclinical studies, CFT7455 has demonstrated potent and selective protein degradation with favorable pharmacological properties. The Company initiated a Phase 1/2 clinical trial for CFT7455 in June 2021. More information about this trial may be accessed at www.clinicaltrials.gov (identifier: NCT04756726).