On March 30, 2020 Cardax, Inc. (OTCQB:CDXI) reported its 2019 results (Press release, Cardax Pharmaceuticals, MAR 30, 2020, View Source [SID1234556015]). Highlights:

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

CHASE Clinical Trial. On September 23, 2019, the Company announced findings from the pre-specified interim review of its ongoing CHASE (Cardiovascular Health Astaxanthin Supplement Evaluation) clinical trial. The CHASE clinical trial is a double-blind, randomized, placebo-controlled clinical trial evaluating the effect of the Company’s astaxanthin dietary supplement ZanthoSyn, on cardiovascular health, as measured by C-Reactive Protein or "CRP" levels in subjects with documented cardiovascular risk factors. Pre-specified secondary cardiovascular and inflammatory health markers, safety parameters, exploratory endpoints, and pre-specified sub-groups are also being assessed.

The interim review included several key cardiovascular health markers: CRP, triglycerides, total cholesterol, LDL cholesterol, oxidized LDL cholesterol, and blood pressure. The results demonstrated pleiotropic effects and excellent safety, which the Company believes provide further mechanistic support for its astaxanthin pharmaceutical development program, the basis for additional patent filings, and support for the cardiovascular health benefits of ZanthoSyn.*

The CHASE clinical trial recently suspended recruitment of new subjects and study visits for existing subjects due to the coronavirus disease 2019 (COVID-19) pandemic and the related governmental "stay-at-home" orders. The Company expects to resume clinical trial operations when permissible and safe to proceed.

Intellectual Property. The Company filed additional patents in 2019 that if issued would extend its patent coverage to 2040 for the composition of matter of CDX-101, the Company’s lead pharmaceutical candidate, and 2039 for certain cardiovascular uses based on the CHASE clinical trial results.

ZanthoSyn Net revenues rebounded with $500,586 in the second half of 2019 compared to $210,363 in the first half of the year. The rebound was primarily driven by a stronger correlation of inventory sell-in/sell-through patterns by the Company’s largest customer, General Nutrition Corporation ("GNC"). ("Sell-in" is defined as wholesale orders of ZanthoSyn by GNC. "Sell-through" is defined as retail sales of ZanthoSyn to GNC customers.)

Financial Results. The Company raised financing of $3,360,000 in 2019 vs. $1,244,037 (net) in 2018 using a combination of convertible notes, equity units (stock and warrants), and loans, the proceeds of which were used for general working capital and to fund research, development, and clinical programs.

Net losses increased to $5,093,037 in 2019 from $4,024,222 in 2018 primarily due to non-cash expenses related to convertible notes issued in 2019, including interest expenses and changes in derivative liability amounts. The loss from operations of $4,077,103 in 2019 was nearly unchanged from $4,022,495 in 2018.

Net revenues decreased to $710,949 in 2019 vs. $1,510,875 in 2018 primarily due to the decrease in GNC replenishment orders of ZanthoSyn in the first half of 2019 following larger stocking orders in 2018. Inventory sell-in/sell-through patterns were more strongly correlated in the second half of 2019.

Subsequent Events. Cardax released a white paper and accompanying press release on March 20, 2020 outlining the potential role of astaxanthin in the treatment of COVID-19 and is seeking strategic collaborations to further develop astaxanthin for COVID-19, including clinical trials. A provisional patent covering this use was also filed.

The Company believes that its financing, including any public or private offerings, and revenues may be affected in 2020 by the COVID-19 pandemic, although the extent of the impact is uncertain at this time.

Cardax raised $770,000 in Q1 2020, of which $150,000 was used to pay off a convertible note due in March 2020, and the balance is being used for general working capital.

"We believe the encouraging CHASE trial interim results and our new patent filings were important accomplishments in 2019. These milestones reflect the successful execution of key parts of our strategy to create value around our pharmaceutical development programs," said David G. Watumull, Cardax CEO. "On the consumer side of the business, we were glad to see the rebound in ZanthoSyn sales in the second half of 2019."

On March 30, 2020 ISA Pharmaceuticals reported that Just weeks after International Human Papilloma Virus (HPV) Awareness Day, new results from two long-time Cancer Research Institute (CRI) scientists highlighted the promise of immunotherapy against HPV-associated cervical cancer (Press release, ISA Pharmaceuticals, MAR 30, 2020, View Source [SID1234555973]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

In a phase 1/2 study, women with advanced, recurrent, or metastatic cervical cancer were treated with the combination of an HPV-targeting vaccine and standard-of-care chemotherapy. Of 72 evaluable patients, 43 percent had their tumors shrink.

Led by Cornelis J. M. Melief, M.D, Ph.D., and Sjoerd H. van der Burg, Ph.D., this clinical breakthrough was the latest fruit borne by the duo, both of whom have been supported by CRI during their time at Leiden University Medical Center in the Netherlands. In addition to being a member of the CRI Scientific Advisory Council, Melief was the recipient of the 2019 AACR (Free AACR Whitepaper)-CRI Lloyd J. Old Award in Cancer Immunology and is currently the chief scientific officer at ISA Pharmaceuticals. Van der Burg, who earned his doctorate in Melief’s lab in 1998, is also affiliated with ISA as a member of their Scientific Advisory Board, as well as the Oncode Institute.

In 2002, CRI-funded preclinical work by Melief and van der Burg provided an early proof of principle that therapeutic HPV vaccines could eliminate HPV-associated cancers. To do so, they used synthetic long peptide (SLP) vaccines to target the E6/E7 oncoproteins produced by the HPV16 strain.

Next, they demonstrated that HPV-targeting vaccines could clear pre-malignant lesions. However, vaccination wasn’t effective against advanced cancers because of the presence of immunosuppressive myeloid cells. By adding chemotherapy to the treatment regimen, the current study sought to decrease the number of myeloid cells and thereby enable more potent anti-tumor immune responses after vaccination, especially by the immune system’s "killer" T cells.

In many patients, the combination appears to have done just that.

Two weeks after chemotherapy, when patients’ myeloid cells were at their lowest point, varying doses of the ISA-101 vaccine were administered. Half of them also received a molecule called pegylated type 1 interferon that may help boost adaptive immune responses. Overall, about one-third of patients analyzed had low levels of HPV-targeting T cells after chemotherapy alone and prior to vaccination. Post-vaccination, HPV-specific T cell responses were detected at all dose levels, and "the patients with higher than median strength responses survived the best," Melief told CRI.

"These results, provided they are validated in larger trials, could lead to significantly improved care for patients with cervical cancer."

In another ongoing study, this vaccine paired well with checkpoint blockade immunotherapy in patients with advanced head and neck cancer—another cancer linked to HPV infection. A similar trial will soon be testing that approach in cervical cancer, according to Melief, who believes we might benefit from going even further with vaccine combinations.

"Last year, we demonstrated the synergy between vaccination and anti-PD-1 checkpoint immunotherapy in patients with recurrent or metastatic HPV+ head and neck cancer. It is therefore tempting to combine all three therapeutic measures—anti-PD-1, vaccination, and chemotherapy—for additional synergy because chemotherapy and anti-PD-1 act by non-overlapping mechanisms. This chemotherapy combination also pinches in nicely with other types of immunotherapy because many types of late-stage cancer induce this kind of myeloid cell-mediated immunosuppression in patients."

On March 30, 2020 Mersana Therapeutics, Inc. (NASDAQ:MRSN), a clinical-stage biopharmaceutical company focused on discovering and developing a pipeline of antibody-drug conjugates (ADCs) targeting cancers in areas of high unmet medical need, reported updated efficacy and safety data in patients with ovarian cancer and non-small cell lung cancer (NSCLC) adenocarcinoma from its ongoing Phase 1 dose escalation study evaluating XMT-1536 (Press release, Mersana Therapeutics, MAR 30, 2020, View Source [SID1234555998]). The Company will host a call today, Monday, March 30, 2020, at 5:00 pm ET during which investigator Debra L. Richardson, MD, Associate Professor of Gynecologic Oncology at the Stephenson Cancer Center at the University of Oklahoma Health Sciences Center and the Sarah Cannon Research Institute and members of the Mersana executive team will present and discuss these data.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"These data demonstrate that XMT-1536, our first-in-class Dolaflexin ADC targeting NaPi2b, delivers confirmed responses and durable stable disease in heavily pretreated ovarian cancer and NSCLC adenocarcinoma patients who have exhausted all other treatment options. These data also show that XMT-1536 is well tolerated without the severe toxicities of other ADC platforms such as neutropenia, neuropathy and ocular toxicity. Moreover, these data establish the potential for a biomarker-response relationship to identify patients most likely to benefit from XMT-1536," said Anna Protopapas, President and Chief Executive Officer of Mersana Therapeutics. "We look forward to advancing XMT-1536 for both ovarian cancer and NSCLC adenocarcinoma patients. Having already accumulated meaningful patient experience in the expansion cohorts, we remain on track to provide an interim update in the second quarter of 2020."

Of the 59 patients enrolled, tumor types included 37 ovarian cancer, 11 NSCLC adenocarcinoma, and 11 other tumor types previously disclosed at lower dose levels. Patients were heavily pre-treated, with a median of five prior lines of treatment (range 1-10). These data include new patients dosed at 30, 36 and 43 mg/m2. The majority of the ovarian cancer patients had received prior bevacizumab or PARP inhibitors. All NSCLC adenocarcinoma patients had received prior platinum and immunotherapy. Updated and new data as of February 3, 2020 includes:

·Safety profile consistent with previously reported data at lower doses.
oThe most common treatment-related adverse events (TRAEs) were Grade 1-2 nausea, fatigue, headache and the most frequent Grade 3 TRAE was transient AST elevation.
oThere were no dose limiting toxicities observed in the 43 mg/m2 cohort.
oThere was no reported severe neutropenia, peripheral neuropathy or ocular toxicity.

·Additional confirmed responses in heavily pretreated patients and favorable biomarker-response trend observed.
oFirst confirmed partial response seen in a NSCLC adenocarcinoma patient with prior treatments including carboplatin, pemetrexed, paclitaxel and nivolumab.
oAt the 43 mg/m2 dose level, 2/7 (29%) patients achieved partial responses (PRs) and 4/7 (57%) patients achieved stable disease (SD) for a disease control rate (DCR) of 6/7 (86%). In January 2020, the expansion portion of the Phase 1 study dose was amended from 36 mg/m2 to 43 mg/m2 for newly enrolled patients.
oFor the subset of evaluable patients treated at >30 mg/m2 who had higher NaPi2b expression, 5/15 (33%) achieved PR and 6/15 (40%) achieved SD for a DCR of 11/15 (73%).
oIn contrast, for the subset of evaluable patients treated at >30 mg/m2 who had lower NaPi2b expression, 0/9 (0%) achieved PR and 5/9 (55%) achieved SD for a DCR of 5/9 (55%).

Response – Ovarian Cancer
and NSCLC
adenocarcinoma N=39* N (%)
All Higher
NaPi2b o Lower
NaPi2b oo Indeterminate
NaPi2b **
20 mg/m2 N 10 7 2 1
PR 1 (10%) 0 (0%) 0 (0%) 1 (100%)
SD 6 (60%) 4 (57%) 2 (100%) 0 (0%)
DCR (PR+SD) 7 (70%) 4 (57%) 2 (100%) 1 (100%)
30, 36, 40 mg/m2 N 22 12 7 3
PR 3 (14%) 3 (25%) 0 (0%) 0 (0%)
SD 10 (45%) 6 (50%) 3 (43%) 1 (33%)
DCR (PR+SD) 13 (59%) 9 (75%) 3 (43%) 1 (33%)
43 mg/m2 N 7 3 2 2
PR 2 (29%) 2 (67%) 0 (0%) 0 (0%)
SD 4 (57%) 0 (0%) 2 (100%) 2 (100%)
DCR (PR+SD) 6 (86%) 2 (67%) 2 (100%) 2 (100%)

*Excludes 3 patients discontinued due to investigator/patient choice and 1 without RECIST scan

**Hypocellular specimen/indeterminate for H-score or not determined yet

O Higher NaPi2b Expression: at / above lowest H-score at which response observed (>110)

OO Lower NaPi2b Expression: below the lowest H-score at which response observed (<110)

Mersana plans to enroll approximately 45 patients in each of the ovarian cancer and NSCLC adenocarcinoma patient cohorts in the expansion portion of the XMT-1536 Phase 1 study. The Company expects to present interim data from the dose expansion study in the second quarter of 2020.

Conference Call Details

Mersana Therapeutics will host a conference call and webcast today at 5:00 p.m. ET to review these data. To access the call, please dial 877-303-9226 (domestic) or 409-981-0870 (international) and provide the Conference ID 2889994. A live webcast of the presentation will be available on the Investors & Media section of the Mersana website at www.mersana.com.

On March 30, 2020 Alphamab Oncology (stock code: 9966HK) reported that Jiangsu Alphamab Biopharmaceuticals Co., Ltd. ("Jiangsu Alphamab"), a wholly-owned subsidiary of the Company, has established strategic partnership with Simcere and 3D Medicines (Beijing) Co., Ltd. ("3DMed") to advance the development and commercialization of KN035 (also known as envafolimab), a checkpoint inhibitor for programmed cell death ligand-1 (PD-L1), for oncology indications in mainland China (Press release, Alphamab, MAR 30, 2020, View Source [SID1234556016]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Under the terms of the agreement, Alphamab Oncology is the exclusive manufacturer of KN035 and responsible for the production and supply of KN035. 3DMed will oversee KN035’s clinical development, registration and commercialization. Simcere will exclusively market KN035 in mainland China upon the product’s registration, and charge a marketing fee to 3DMed.

Invented by Alphamab Oncology, KN035 is a recombinant anti-PD-L1 single domain antibody fused with human Fc. In 2016, Alphamab Oncology and 3DMed reached an agreement to co-develop KN035 which is on track to be the first subcutaneous injectable anti-PD1/PD-L1 antibody to be approved globally. Compared to other marketed PD1/PD-L1 antibodies, KN035 has demonstrated distinctive advantages in safety, convenience and patient compliance, which may further improve patients’ quality of life. KN035 is undergoing clinical trials in China, the United States, and Japan for multiple cancer indications, with more than 900 patients enrolled, including a pivotal Phase II clinical trial investigating the treatment of advanced solid tumors with microsatellite instability-high (MSI-H)/mismatch repair deficiency (dMMR). Additionally, KN035 is undergoing pivotal Phase III clinical trials for advanced biliary tract cancer (BTC) in China. On January 18, 2020, KN035 was granted FDA Orphan Drug Designation (ODD) for the treatment of advanced biliary tract cancer (BTC).

Dr. Ting XU, Founder, Chairman and CEO of Alphamab Oncology, commented, "KN035 is likely the first PD-L1 inhibitor with subcutaneous administration to be approved globally. Compared to PD-1/PD-L1 drugs on the market currently, it has strong differentiation and advantages including stability, compliance, convenience and cost. KN035 is one of our many globally competitive innovative candidates as a result of our relentless R&D effort by focusing on globally innovative biologics for over a decade. To certain extent, this also represents the trend that Chinese pharmaceutical companies are becoming more competitive in global innovation. And this collaboration amongst three companies not only has demonstrated how top tier innovative R&D, clinical and commercial teams in China join forces, but also could set the example of an outstanding collaboration of innovative drug R&D and commercialization in China aiming to benefit more cancer patients in the near future."

Mr. Jinsheng REN, Founder and Chairman of Simcere, added: "KN035 is a first-in-class single domain PD-L1 antibody. With distinctive characteristics and advantages such as subcutaneous injection and stability at room temperature, KN035 can improve compliance and the quality of life of cancer patients, and simultaneously may reduce medical costs and improve drug accessibility. It is a medication with greater clinical significance and can truly benefit patients and our society. This strategic partnership will enable synergy in early stage development, clinical development, and commercialization. Together, we hope to fulfill our mission of making better medicines available to patients sooner."

Dr. Zhaolong GONG, Chairman and CEO of 3DMed added, "We are pleased to reach a major partnership with Simcere, a company with a well-established marketing network and in-depth experience in the China market, to drive the development and commercialization of KN035 in oncology. In addition to the indications being investigated, we will fully leverage KN035’s distinctive differentiation advantages in convenience and safety features, by pursuing clinical development of KN035 in the first line treatment of advanced stage cancer, in maintenance therapy, in adjuvant and neo-adjuvant treatment, with the aim of providing better treatment options for cancer patients worldwide."

On March 30, 2020 Rhythm Pharmaceuticals, Inc. (Nasdaq: RYTM), a late-stage biopharmaceutical company aimed at developing and commercializing therapies for the treatment of rare genetic disorders of obesity, reported that Hunter Smith, the Company’s Chief Financial Officer, has been named to the additional role of Interim Chief Executive Officer, effective immediately (Press release, Rhythm Pharmaceuticals, MAR 30, 2020, View Source [SID1234556041]). Mr. Smith succeeds Keith Gottesdiener, M.D. whose planned departure was announced by the Company in January 2020. Dr. Gottesdiener stepped down from his roles as CEO, President and member of the Board of Directors following the Company’s completion of its New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

"On behalf of the Board, I am pleased that Hunter and the Rhythm management team will continue their excellent stewardship of the Company and dedication to transforming the care of people living with rare genetic disorders of obesity while we continue our search for a permanent CEO," said David Meeker, M.D., Chairman of the Board of Directors. "With Murray Stewart, Chief Medical Officer, leading our clinical development and regulatory strategy and Nithya Desikan, Chief Commercial Officer, and her team making tremendous strides in community building, we believe that Rhythm is well positioned to change the paradigm for rare genetic obesity."

As previously disclosed, the Company’s Board of Directors has formed a search committee and retained an executive search firm to assist in identifying Dr. Gottesdiener’s permanent successor. The Board has made significant progress in the search process and is considering a number of highly qualified candidates.

"I look forward to working closely with the Board, Murray and Nithya, our colleagues on the management team, and the entire Rhythm team to advance setmelanotide," Mr. Smith said. "We are committed to working with patients and the community to build greater awareness and understanding of rare genetic disorders of obesity so we can maximize our impact and transform the care of people living with these conditions."

COVID-19 and Business Continuity
To help protect the health and safety of the patients, caregivers and healthcare professionals involved in its ongoing clinical trials of setmelanotide, as well as its employees, in response to the novel coronavirus (COVID-19) pandemic, Rhythm has implemented a number of precautionary clinical and operational measures to protect patient well-being and ensure consistent and appropriate clinical trial conduct.

With many clinical trial sites already closing down in response to COVID-19-related country- and state-level guidelines and more closures expected, Rhythm and study investigators and staff remain focused on the safety, treatment and monitoring of patients currently enrolled in these trials. Rhythm has introduced measures to ensure patients in ongoing clinical trials continue to be monitored as scheduled and receive their study drug.

Mr. Smith continued, "We are acutely aware of the unprecedented crisis unfolding across the globe as a result of the COVID-19 pandemic. Over the past several weeks, we have put measures in place to protect the health and safety of patients and staff participating in our clinical trials, as well as our employees and their families, and to seek to ensure that our ongoing studies can continue with minimal interruption."

POMC Deficiency Obesity and LEPR Deficiency Obesity
Today, Rhythm announced that it has completed its rolling submission of an NDA to the FDA for setmelanotide for the treatment of pro-opiomelanocortin (POMC) deficiency obesity and leptin receptor (LEPR) deficiency obesity. The FDA typically has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing. Rhythm has requested priority review for the application which, if granted, could provide a target FDA review period of six months from the application filing date. Rhythm continues to anticipate that it will submit a Marketing Authorization Application (MAA) to the European Medicines Agency (EMA) in the second quarter of 2020. At this time, Rhythm is continuing its regular interactions with the FDA and EMA and based on current information, the Company does not anticipate COVID-19 to materially affect its timelines.

Ongoing Clinical Trials of Setmelanotide
Rhythm continues to expect to meet disclosed timelines for reporting data from its pivotal Phase 3 trial in Bardet-Biedl Syndrome (BBS) and Alström Syndrome and Phase 2 Basket Study. The Company anticipates announcing topline data in the fourth quarter of 2020 or early in the first quarter of 2021 from the Phase 3 BBS and Alström syndrome trial, which completed enrollment in December 2019. Rhythm also anticipates announcing additional data in high-impact heterozygous (HET) obesity and additional data from one or more of its other ongoing indications in 2020, based on current enrollment levels in the Phase 2 Basket Study.

Rhythm currently believes there will be no disruption of clinical supply of setmelanotide. The Company’s contract manufacturers have indicated that they have appropriate plans and procedures in place to ensure uninterrupted future supply of clinical and commercial-grade setmelanotide, subject to potential limitations on their operations due to COVID-19.

Corporate Operations

Consistent with guidelines from the Centers for Disease Control (CDC) and the Commonwealth of Massachusetts, Rhythm has also implemented measures to help keep the Company’s employees, families, and local communities healthy and safe. All employees are working remotely and all business travel has been restricted.