On January 13, 2020 Human Longevity, Inc., an innovator in providing data-driven health intelligence and precision health to physicians and patients reported that the Oncology Division was sold to NeoGenomics (NASDAQ NEO) for $37 Million (Press release, Human Longevity, JAN 13, 2020, View Source [SID1234553107]). The financing, a cash transaction, closed on Friday, January 10, 2020.

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David Karow, MD, PhD, President and Chief Innovation Officer of Human Longevity, Inc., said, "The sale of this division allows us to focus entirely on longevity and extending the healthy, high-performance human lifespan. Additionally, it will provide the firm with additional working capital, along with the recent Series A2 round of financing, to grow domestically and internationally."

On January 13, 2020 John Theurer Cancer Center at Hackensack University Medical Center in New Jersey were part of the CANDOR global phase III clinical trial for patients with refractory (persistent) multiple myeloma (Press release, John Theurer Cancer Center, JAN 13, 2020, View Source [SID1234553124]). The study was selected as the prestigious plenary presentation at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, the world’s leading conference for hematologic cancers and blood disorders, held in Orlando in December.

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The CANDOR study showed that the addition of the anti-CD38 monoclonal antibody daratumumab to treatment with carfilzomib and dexamethasone was more effective than conventional carfilzomib and dexamethasone. Patients receiving the three-drug regimen experienced a 37% reduction in the risk of disease progression or death, establishing a new standard of care. Patients in the CANDOR trial had been heavily pretreated and most had failed to respond to lenalidomide, an immunomodulating drug that forms the backbone of most multiple myeloma treatment regimens.

"In this population, we have had limited choices. This study shows that we can safely combine what are arguably the most active drugs for the treatment of myeloma," explained David Siegel, M.D., Ph.D., founding director of John Theurer Cancer Center’s Multiple Myeloma Institute, who led John Theurer Cancer Center’s involvement in the study. "Treatment with daratumumab, carfilzomib, and dexamethasone represents a new effective regimen for patients with recurrent or persistent multiple myeloma, especially those whose disease came back or continues to grow after lenalidomide therapy."

The phase III CANDOR study included 466 patients with multiple myeloma that persisted despite one to three prior regimens of therapy. Patients were randomly assigned 2:1 to receive either daratumumab, carfilzomib, and dexamethasone or carfilzomib and dexamethasone. After a median follow-up of 17 months, the median progression-free survival was not yet reached in the three-drug combination group, versus 16 months in patients receiving the standard therapy. Patients receiving three drugs had a better overall response rate (84.3% versus 74.7%) and a better rate of complete response or better (28.5% versus 10.4%), and the achievement of undetectable disease was nearly ten times higher (12.5% versus 1.3%). It was too early to detect any differences in overall survival.

On January 13, 2020 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported its preliminary* fourth quarter and full year 2019 global net product revenues for ONPATTRO and GIVLAARI and provided additional updates on the products’ commercial launches (Press release, Alnylam, JAN 13, 2020, View Source [SID1234553146]).

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For ONPATTRO, the Company reported:

Preliminary global net product revenues for the fourth quarter and full year 2019 were approximately $56 million and $166 million, respectively.

As of year-end 2019, over 750 patients worldwide were receiving commercial ONPATTRO, and over 1,000 total patients worldwide were being treated with patisiran, when also including those patients in clinical studies and in the Company’s global Expanded Access Program (EAP).

In the U.S., 44% of Start Forms submitted in 2019 came from cardiologists, 38% from neurologists, and 18% from other physician specialties.

Significant ONPATTRO new patient growth in the fourth quarter was seen in the U.S. and EU, along with a strong launch in Japan.

In the U.S., Alnylam has now completed definitive value-based agreements (VBAs) with 14 commercial payers, including each of the top 5 commercial payers and 8 of the top 10, with signed VBAs now covering over 130 million U.S. lives in the aggregate.

For the period following approval of GIVLAARI in the U.S. on November 20 through year end, the Company reported:

A total of 13 Start Forms were submitted.

Preliminary global net product revenues were approximately $0.2 million representing initial channel stocking.

The Company has made significant progress toward establishing VBAs, including a Prevalence-Based Adjustment feature, with multiple ongoing discussions with payers.

"In 2019 we achieved continued and steady growth of patients on ONPATTRO and we expect sustained growth in 2020 and beyond. We believe our preliminary results reflect strong patient and physician demand and excellent execution by our commercial teams around the world. With the early U.S. approval of GIVLAARI, we are now a multi-product commercial company, and are pleased with the strong initial interest from patients and physicians in the short period since the drug’s approval by the FDA. We’re also encouraged by the receptivity of U.S. payers to the value that GIVLAARI has the potential to deliver," said John Maraganore, Ph.D., Chief Executive Officer of Alnylam. "In 2020, we look forward to the continued launches of ONPATTRO and GIVLAARI, bringing the benefits of these innovative therapies to patients around the world. We also look forward to advancing lumasiran – as our third wholly owned RNAi therapeutic – as well as inclisiran – with our partners at Novartis – toward the market in 2020 and achieving additional milestones across our broad late-stage pipeline of investigational RNAi therapeutics, notably in our ATTR amyloidosis clinical programs."

In addition, the Company today reported that at December 31, 2019, it had preliminary cash, cash equivalents, marketable debt and equity securities, and restricted investments of approximately $1.5 billion, as compared to $1.1 billion at December 31, 2018.

Alnylam management will discuss these preliminary selected financial results and commercial updates during a webcast presentation at the 38th Annual J.P. Morgan Healthcare Conference in San Francisco, California tomorrow, Monday, January 13, 2020, at 10:30 a.m. PT (1:30 p.m. ET).

* The preliminary selected financial results are unaudited, subject to adjustment, and provided as an approximation in advance of the Company’s announcement of complete financial results in February 2020.

About ONPATTRO (patisiran)

ONPATTRO is an RNAi therapeutic that is approved in the United States and Canada for the treatment of the polyneuropathy of hATTR amyloidosis in adults. ONPATTRO is also approved in the European Union and Switzerland for the treatment of hATTR amyloidosis in adults with Stage 1 or Stage 2 polyneuropathy, and in Japan for the treatment of hATTR amyloidosis with polyneuropathy. Based on Nobel Prize-winning science, ONPATTRO is an intravenously

administered RNAi therapeutic targeting transthyretin (TTR). It is designed to target and silence TTR messenger RNA, thereby blocking the production of TTR protein before it is made. ONPATTRO blocks the production of TTR in the liver, reducing its accumulation in the body’s tissues in order to halt or slow down the progression of the polyneuropathy associated with the disease. For more information about ONPATTRO, visit ONPATTRO.com.

ONPATTRO Important Safety Information

Infusion-Related Reactions

Infusion-related reactions (IRRs) have been observed in patients treated with ONPATTRO. In a controlled clinical study, 19 percent of ONPATTRO-treated patients experienced IRRs, compared to 9 percent of placebo-treated patients. The most common symptoms of IRRs with ONPATTRO were flushing, back pain, nausea, abdominal pain, dyspnea, and headache.

To reduce the risk of IRRs, patients should receive premedication with a corticosteroid, acetaminophen, and antihistamines (H1 and H2 blockers) at least 60 minutes prior to ONPATTRO infusion. Monitor patients during the infusion for signs and symptoms of IRRs. If an IRR occurs, consider slowing or interrupting the infusion and instituting medical management as clinically indicated. If the infusion is interrupted, consider resuming at a slower infusion rate only if symptoms have resolved. In the case of a serious or life-threatening IRR, the infusion should be discontinued and not resumed.

Reduced Serum Vitamin A Levels and Recommended Supplementation

ONPATTRO treatment leads to a decrease in serum vitamin A levels. Supplementation at the recommended daily allowance (RDA) of vitamin A is advised for patients taking ONPATTRO. Higher doses than the RDA should not be given to try to achieve normal serum vitamin A levels during treatment with ONPATTRO, as serum levels do not reflect the total vitamin A in the body.

Patients should be referred to an ophthalmologist if they develop ocular symptoms suggestive of vitamin A deficiency (e.g. night blindness).

Adverse Reactions

The most common adverse reactions that occurred in patients treated with ONPATTRO were upper respiratory-tract infections (29 percent) and infusion-related reactions (19 percent).

For additional information about ONPATTRO, please see the full Prescribing Information.

About GIVLAARI (givosiran)

GIVLAARI is an RNAi therapeutic targeting aminolevulinic acid synthase 1 (ALAS1) that is approved in the U.S. for the treatment of adults with acute hepatic porphyria (AHP). In the pivotal study, GIVLAARI was shown to significantly reduce the rate of porphyria attacks that required hospitalizations, urgent healthcare visits or IV hemin administration at home compared to placebo. GIVLAARI is Alnylam’s first commercially available therapeutic based on its Enhanced Stabilization Chemistry (ESC) GalNAc conjugate technology to increase potency and durability. GIVLAARI is administered via subcutaneous injection once monthly at a dose based on actual body weight and should be administered by a healthcare professional. GIVLAARI works by specifically reducing elevated levels of ALAS1 messenger RNA (mRNA), leading to reduction of toxins associated with attacks and other disease manifestations of AHP. For more information about GIVLAARI, visit GIVLAARI.com.

GIVLAARI Important Safety Information

Contraindications

GIVLAARI is contraindicated in patients with known severe hypersensitivity to givosiran. Reactions have included anaphylaxis.

Anaphylactic Reaction

Anaphylaxis has occurred with GIVLAARI treatment (<1% of patients in clinical trials). Ensure that medical support is available to appropriately manage anaphylactic reactions when administering GIVLAARI. Monitor for signs and symptoms of anaphylaxis. If anaphylaxis occurs, immediately discontinue administration of GIVLAARI and institute appropriate medical treatment.

Hepatic Toxicity

Transaminase elevations (ALT) of at least 3 times the upper limit of normal (ULN) were observed in 15% of patients receiving GIVLAARI in the placebo-controlled trial. Transaminase elevations primarily occurred between 3 to 5 months following initiation of treatment.

Measure liver function tests prior to initiating treatment with GIVLAARI, repeat every month during the first 6 months of treatment, and as clinically indicated thereafter. Interrupt or discontinue treatment with GIVLAARI for severe or clinically significant transaminase elevations. In patients who have dose interruption and subsequent improvement, reduce the dose to 1.25 mg/kg once monthly. The dose may be increased to the recommended dose of 2.5 mg/kg once monthly if there is no recurrence of severe or clinically significant transaminase elevations at the 1.25 mg/kg dose.

Renal Toxicity

Increases in serum creatinine levels and decreases in estimated glomerular filtration rate (eGFR) have been reported during treatment with GIVLAARI. In the placebo-controlled study, 15% of patients receiving GIVLAARI experienced a renally-related adverse reaction. The median increase in creatinine at Month 3 was 0.07 mg/dL. Monitor renal function during treatment with GIVLAARI as clinically indicated.

Injection Site Reactions

Injection site reactions were reported in 25% of patients receiving GIVLAARI in the placebo-controlled trial. Symptoms included erythema, pain, pruritus, rash, discoloration, or swelling around the injection site. One (2%) patient experienced a single, transient, recall reaction of erythema at a prior injection site with a subsequent dose administration.

Drug Interactions

Concomitant use of GIVLAARI increases the concentration of CYP1A2 or CYP2D6 substrates, which may increase adverse reactions of these substrates. Avoid concomitant use of GIVLAARI with CYP1A2 or CYP2D6 substrates for which minimal concentration changes may lead to serious or life-threatening toxicities. If concomitant use is unavoidable, decrease the CYP1A2 or CYP2D6 substrate dosage in accordance with approved product labeling.

Adverse Reactions

The most common adverse reactions that occurred in patients receiving GIVLAARI were nausea (27%) and injection site reactions (25%).

For additional information about GIVLAARI, please see full Prescribing Information.

About LNP Technology

Alnylam has licenses to Arbutus Biopharma LNP intellectual property for use in RNAi therapeutic products using LNP technology.

About RNAi

RNAi (RNA interference) is a natural cellular process of gene silencing that represents one of the most promising and rapidly advancing frontiers in biology and drug development today. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and was recognized with the award of the 2006 Nobel Prize for Physiology or Medicine. By harnessing the natural biological process of RNAi occurring in our cells, a new class of medicines, known as RNAi therapeutics, is now a reality. Small interfering RNA (siRNA), the molecules that mediate RNAi and comprise Alnylam’s RNAi therapeutic platform, function upstream of today’s medicines by potently silencing messenger RNA (mRNA) – the genetic precursors – that encode for disease-causing proteins, thus preventing them from being made. This is a revolutionary approach with the potential to transform the care of patients with genetic and other diseases.

On January 13, 2020 TIO Bioventures, an emerging life science venture creation fund with a mission to build companies with innovative anti-cancer therapies, reported the launch of Treadwell Therapeutics, a clinical-stage oncology company exploiting cancer cells’ vulnerabilities to develop first-in-class and best-in-class small molecules to address unmet needs in patients with cancer (Press release, Tio Bioventures, JAN 13, 2020, View Source [SID1234553221]). Treadwell, one of TIO Bioventures family of companies launched from its discovery engine, TIO Discovery, was established with an initial $27 million in seed financing from TIO Bioventures to develop a robust pipeline of novel, first-in-class, small molecule drug candidates.

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"At Treadwell, we are developing small molecules designed to leverage world-class, innovative science in cancer biology and immune-oncology with pan-cancer potential, including hematological malignancies from the TIO Discovery development engine," said Dr. Michael Tusche, Treadwell Co-Chief Executive Officer and Partner at TIO Bioventures.

The origins of Treadwell lie in cutting-edge research incubated at the Campbell Family Institute for Breast Cancer Research (CFIBCR) within the University Health Network (UHN), Canada’s largest research hospital. Based on this research, Treadwell scientists have designed and advanced from discovery to Phase 2 clinical development, a first-in-class PLK4 kinase inhibitor, CFI-400945 and a potentially best-in-class TTK inhibitor, CFI-402257. These candidates have demonstrated encouraging safety and efficacy profiles in multiple investigator-sponsored clinical trials. In addition, Treadwell is poised to bring a third molecule into the clinic in early 2020. This agent, CFI-402411, an oral immunomodulatory kinase inhibitor with activity toward HPK1, an untapped immune-oncology target. Preclinical studies have demonstrated the promise of CFI-402411 as a potential monotherapy and in combination with existing checkpoint inhibitors across both solid and hematological cancers. Treadwell’s product candidates are wholly-owned and have been developed in TIO Discovery, a unique R&D engine wholly owned by TIO.

Leadership

The Company announced the appointment of Rachel W. Humphrey, M.D., as Head of R&D at TIO Discovery as well as Chief Medical Officer and Board Member at Treadwell. Dr. Humphrey joins TIO Bioventures and Treadwell with over two decades of experience as a senior clinical leader in oncology drug development for both large pharmaceutical and emerging biotechnology companies. Her experience includes overall leadership of the clinical development of Yervoy (ipilmumab), the first FDA approved checkpoint inhibitor, at Bristol-Myers Squibb, the development of Imfinzi (durvalumab) at Astra Zeneca and the development of Nexavar (sorafenib) at Bayer, as primary driver of the vision, science and direction during critical periods in the development for these transformational medicines.

"TIO Bioventures novel approach to found, launch, and support companies such as Treadwell speaks to this powerful and successful relationship of world-class scientists with deeply experienced management executives, and I am delighted to join Treadwell at such a pivotal time in the Company’s growth," said Dr. Humphrey. "I look forward to working with the team to further drive the development of these candidates with encouraging anti-cancer activity and exciting novel targets."

She will join Treadwell Therapeutics’ existing leadership team composed of world-class experts in immunology and oncology drug development, including Dr. Tak Mak, co-founder and managing partner of TIO Bioventures, who has led the development of multiple successful biotechnology companies.

On January 13, 2020 Hutchison China MediTech Limited ("Chi-Med") (AIM/Nasdaq: HCM) reported that it has initiated a Phase II study in China of surufatinib in combination with Tuoyi (toripalimab) in patients with advanced solid tumors (Press release, Hutchison China MediTech, JAN 13, 2020, https://www.chi-med.com/chi-med-initiates-a-phase-ii-trial-of-surufatinib-in-combination-with-tuoyi-in-patients-with-advanced-solid-tumors/ [SID1234553057]). This follows the recent completion of the Phase I dose finding study and successful establishment of the Phase II combination dosing regimen for surufatinib and Tuoyi.

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This China Phase II clinical study is part of a global collaboration with Shanghai Junshi Biosciences Co. Ltd. ("Junshi"), to evaluate surufatinib, Chi-Med’s oral angio-immuno kinase inhibitor, in combination with Tuoyi, Junshi’s anti-programmed cell death protein 1 ("PD-1") monoclonal antibody which was approved by China’s National Medical Products Administration ("NMPA") in December 2018. The study is designed to test the potential synergistic anti-tumor effects of the combination’s ability to simultaneously target multiple cell types and signaling pathways in the tumor microenvironment.

The Phase II study plans to explore multiple solid tumor patient populations. The primary outcome measures are objective response rate (ORR) and safety. The secondary outcomes include duration of response (DoR), progression-free survival ("PFS"), disease control rate (DCR) and overall survival ("OS"). The lead principal investigator of the study is Professor Lin Shen, Vice President of Peking University Hospital and Cancer Institute. Additional details may be found at clinicaltrials.gov, using identifier NCT04169672.

Christian Hogg, Chief Executive Officer of Chi-Med, said, "We are excited to move into Phase II development on the surufatinib toripalimab combination and look forward to identifying patient groups that could benefit from this innovative treatment regimen."

In December 2019, surufatinib was granted Priority Review status by the Center for Drug Evaluation (CDE) of China’s NMPA for its New Drug Application ("NDA") for the treatment of patients with advanced non-pancreatic neuroendocrine tumors ("NET").

In November 2019, the NDA for surufatinib for the treatment of non-pancreatic NET was accepted for review by the NMPA, and the U.S. Food and Drug Administration granted Orphan Drug designation to surufatinib for the treatment of pancreatic NET.

About Surufatinib
Surufatinib (previously known as HMPL-012 or sulfatinib) 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. Surufatinib is in several late-stage and proof-of-concept clinical trials in China and proof-of-concept clinical trials in the U.S.

According to Frost & Sullivan, the market for anti-angiogenesis VEGF/VEGFR inhibitors in China has grown from US$500 million in 2015 to over US$1.5 billion in 2019 and is expected to reach US$5 billion by 2026.

Chi-Med currently retains all rights to surufatinib worldwide.

Non-Pancreatic NET in China: In 2015, we initiated the SANET-ep study, a Phase III study of surufatinib in advanced neuroendocrine tumors – extra-pancreatic patients in China for whom there is no effective therapy. In June 2019, a 198-patient interim analysis was conducted, leading the independent data monitoring committee to determine that the study met the pre-defined primary endpoint of progression-free survival ("PFS") and should be stopped early. The positive results were highlighted in an oral presentation at the 2019 European Society for Medical Oncology Congress in September 2019. In November 2019, the NDA was accepted for review by the NMPA (clinicaltrials.gov identifier: NCT02588170) and subsequently granted Priority Review status.

Pancreatic NET in China: In 2016, we initiated the SANET-p study, which is a pivotal Phase III study in patients with low- or intermediate-grade, advanced pancreatic NET in China. The primary endpoint is PFS. We expect an interim analysis in the first half of 2020 and enrollment to complete in 2020 (clinicaltrials.gov identifier: NCT02589821).

NET in the U.S. and Europe: We are planning a U.S. registration study in NET patients based on the encouraging data from the Phase II and Phase III studies of surufatinib in NET in China (clinicaltrials.gov identifier: NCT02267967), and the ongoing Phase II study in the U.S. (clinicaltrials.gov identifier: NCT02549937).

Biliary tract cancer in China: In March 2019, we 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: In November 2018 and September 2019, we entered into collaboration agreements to evaluate the safety, tolerability and efficacy of surufatinib in combination with anti-PD-1 monoclonal antibodies. This included global collaborations to evaluate the combination of surufatinib with Tuoyi, approved in China by Junshi, and with Tyvyt, approved in China by Innovent Biologics, Inc.