HUTCHMED Initiates Phase II Registration Study of HMPL-689 in Patients with Follicular Lymphoma and Marginal Zone Lymphoma in China

On April 29, 2021 Hutchison China MediTech Limited ("HUTCHMED") (Nasdaq/AIM: HCM) reported that it has initiated a registration-intent Phase II clinical trial of HMPL-689, its highly selective and potent PI3Kδ inhibitor, in China in patients with relapsed or refractory follicular lymphoma ("FL") and marginal zone lymphoma ("MZL"), two subtypes non-Hodgkin’s lymphoma ("NHL") (Press release, Hutchison China MediTech, APR 29, 2021, View Source [SID1234583630]). The first patient was dosed today .

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The clinical trial is a multi-center, single-arm, open-label clinical study to evaluate the efficacy and safety of HMPL-689 once a day oral monotherapy in approximately 100 patients with relapsed/refractory FL and approximately 80 patients with relapsed/refractory MZL. Relapsed/refractory is defined when a patient has not achieved response (complete response or partial response) after the latest line of systemic treatment, or has progressive disease or relapse after achieving response. The primary endpoint is objective response rate ("ORR"), with secondary endpoints including complete response rate (CRR), progression-free survival (PFS), time to response (TTR) and duration of response (DoR). The trial is being conducted in over 35 sites in China. More information will be available at clinicaltrials.gov, using identifier NCT04849351.

The initiation of the Phase II trial is based on the highly promising preliminary results from the Phase Ib expansion study ongoing in China, which show that HMPL-689 was well tolerated, exhibiting dose-proportional pharmacokinetics ("PK"), a manageable toxicity profile, and single-agent clinical activity in relapsed/refractory B-cell lymphoma patients. Additional details may be found at clinicaltrials.gov, using identifier NCT03128164.

About PI3Kδ and NHL

PI3Kδ (phosphoinositide 3-kinase delta) is a lipid kinase that controls the activation of several important signaling proteins. Upon an antigen binding to B-cell receptors, PI3Kδ can be activated through the Lyn and Syk signaling cascade. The abnormal activation of B-cell receptor signaling is closely related to the development of B-cell type hematological cancers, which represent approximately 85% of all NHL cases. Therefore, PI3Kδ is considered to be a promising target for drugs that aim to prevent or treat hematologic cancer.

FL accounts for approximately 17% of NHL and MZL accounts for approximately 8% of NHL. In the U.S., there were estimated 13,000 and 6,000 new cases of FL and MZL in 2020, respectively. In China, there were estimated 16,000 and 7,000 new cases of FL and MZL in 2020, respectively 1,2,3.

About HMPL-689

HMPL-689 is a novel, selective and potent oral inhibitor targeting the isoform PI3Kδ. HMPL-689’s PK properties are favorable with good oral absorption, moderate tissue distribution and low clearance in preclinical PK studies, suggesting a low risk of drug accumulation and drug-to-drug interaction. Because of its high target selectivity and optimal PK profile, HMPL-689 has the potential to demonstrate an optimal benefit-risk profile in this class.

HUTCHMED has initiated an extensive, globally-focused clinical development pathway for HMPL-689. In addition to the currently Phase II trial and the supportive Phase I trial in China, HMPL-689 is also being evaluated in an ongoing Phase I/Ib study in the U.S. and Europe in patients with relapsed or refractory NHL.

HUTCHMED currently retains all rights to HMPL-689 worldwide.

Results of Operations and Financial Condition

On April 29, 2021, Acceleron Pharma reported that Bristol Myers Squibb ("BMS") has announced net sales of REBLOZYL (luspatercept-aamt) to be approximately $112 million for the quarter ended March 31, 2021. As previously disclosed, under the collaboration agreement between Acceleron Pharma Inc. (the "Company") and BMS for REBLOZYL, the Company is eligible to receive tiered royalty payments from BMS on net sales of REBLOZYL in the low-to-mid 20% range. The Company expects to report royalty revenue of approximately $22.4 million from net sales of REBLOZYL in the quarter ended March 31, 2021.

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This preliminary unaudited revenue estimate is the responsibility of management and is subject to the completion of the Company’s customary quarter-end financial closing procedures, including management’s review and finalization, as well as review procedures by the Company’s independent registered public accounting firm, which have not yet been completed. During the course of the Company’s review process, items may be identified that would require it to make adjustments, which could result in material changes to the Company’s preliminary unaudited estimated financial results. Consequently, this revenue estimate should not be viewed as a substitute for the Company’s earnings release and the Quarterly Report on Form 10-Q for the quarter ended March 31, 2021.

The information contained in this Item is being furnished and shall not be deemed "filed" for any purpose, and shall not be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, regardless of any general incorporation language in any such filing.

MacroGenics Provides Update on Corporate Progress and First Quarter 2021 Financial Results

On April 29, 2021 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported an update on its recent corporate progress and reported financial results for the quarter ended March 31, 2021 (Press release, MacroGenics, APR 29, 2021, View Source [SID1234578756]).

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"With the recent launch and commercialization of MARGENZA, we are delivering on our vision to provide potentially life-changing therapeutics to patients with cancer. We are well positioned to advance this mission as the growing body of data emerges from our deep pipeline of clinical and pre-clinical product candidates," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics, "and we look forward to sharing additional data with you as the year progresses."

Key Updates on Proprietary Programs

Recent progress and anticipated events in 2021 related to MacroGenics’ approved and investigational product candidates in clinical development are highlighted below.

Margetuximab is an Fc-engineered, monoclonal antibody (mAb) that targets the HER2 oncoprotein, which is expressed by certain breast, gastroesophageal and other solid tumor cells.

MARGENZA (margetuximab-cmkb) commercial launch. In mid-March 2021, MacroGenics and its commercial partner, EVERSANA, launched MARGENZA for the treatment of adult patients with metastatic HER2-positive breast cancer, in combination with chemotherapy, who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Also during the quarter, results from the SOPHIA metastatic breast cancer Phase 3 study of MARGENZA were published in the Journal of the American Medical Association (JAMA) Oncology. Finally, based on the current accrual rate of overall survival (OS) events in the ongoing SOPHIA trial that supported approval by the FDA, the Company now anticipates completing the final analysis of OS data, based on accrual of the 385th OS event, by the end of the third quarter.

Phase 2/3 MAHOGANY study in advanced gastric and gastroesophageal junction cancer. The MAHOGANY clinical program contains two modules designed to evaluate margetuximab as an investigational agent in combination with a checkpoint inhibitor, with or without chemotherapy, as a potential first-line treatment for patients with advanced or metastatic HER2-positive GC/GEJ. All 40 patients have been enrolled in the first part of Module A, which is evaluating margetuximab in combination with retifanlimab (an anti-PD-1 therapy). The Company expects to report safety and efficacy data in the third quarter of 2021. Enrollment in Module B, which is evaluating margetuximab plus MacroGenics’ checkpoint inhibitor molecules in combination with chemotherapy compared to standard of care therapy of trastuzumab with chemotherapy in patients with HER2-positive tumors irrespective of PD-L1 expression, is currently ongoing in coordination with MacroGenics’ regional partner in Greater China, Zai Lab.

Flotetuzumab is a bispecific CD123 × CD3 DART molecule being evaluated in patients with primary induction failure (PIF) and early relapsed (less than six months, or ER6) acute myeloid leukemia (AML). MacroGenics is conducting a single-arm, registration-enabling clinical study to evaluate flotetuzumab in up to 200 patients with PIF/ER6 AML, with complete remission (CR) and CR with partial hematological recovery (CRh) as the composite primary endpoint. The Company anticipates providing further updates on the clinical development of flotetuzumab in late 2021 and completing full enrollment of this study in 2022.

MGC018 is an antibody-drug conjugate (ADC) that targets B7-H3. In April 2021, MacroGenics presented pre-clinical data at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting demonstrating that at clinically relevant dose levels, MGC018 potentiated antitumor activity in vivo in mouse patient-derived xenograft (PDX) models of squamous cell carcinoma of the head and neck (SCCHN). MacroGenics recently expanded its Phase 1 clinical study to include SCCHN and melanoma; the Company continues to enroll patients with metastatic castration-resistant prostate cancer (mCRPC), triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). MacroGenics will provide a clinical data update via poster presentation at the upcoming American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) 2021 Annual Meeting, June 4-8, 2021.

Enoblituzumab is an Fc‐engineered, anti‐B7‐H3 mAb. During the first quarter, MacroGenics initiated a Phase 2 study of enoblituzumab in a chemotherapy-free regimen in combination with retifanlimab in front-line patients with SCCHN who are PD-L1 positive and with tebotelimab in SCCHN patients who are PD-L1 negative.
Tebotelimab is a bispecific, tetravalent DART molecule targeting PD-1 and LAG-3. Tebotelimab is being evaluated in a Phase 1 dose expansion study as monotherapy in several tumor types. MacroGenics expects to provide updates on the next-stage of development for tebotelimab later this year.

MGD019 is a bispecific, tetravalent DART molecule targeting PD-1 and CTLA-4. The Company is conducting Phase 1 dose expansion cohorts at the recommended Phase 2 dose in patients with microsatellite stable colorectal cancer (MSS CRC) and checkpoint-naïve NSCLC and recently added cohorts of patients with mCRPC and melanoma.

IMGC936 is an ADC that targets ADAM9, a cell surface protein over-expressed in several solid tumor types, and is being developed jointly under a 50/50 collaboration with ImmunoGen, Inc. Pre-clinical data recently presented at the AACR (Free AACR Whitepaper) Annual Meeting showed that IMGC936 had activity against multiple solid tumor types in in vivo mouse PDX models. Under the collaboration, ImmunoGen is leading clinical development of IMGC936 in a Phase 1 clinical trial evaluating safety and pharmacokinetics in patients with select cancers and have indicated they anticipate disclosing initial data by early 2022.

MGD024 is a next-generation, bispecific CD123 × CD3 DART molecule in preclinical development. The molecule incorporates a CD3 component designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, along with an Fc domain to permit intermittent dosing through a longer half-life. The Company anticipates submitting an Investigational New Drug (IND) application to the FDA by the end of 2021.

First Quarter 2021 Financial Results

Cash Position: Cash, cash equivalents and marketable securities as of March 31, 2021, were $343.2 million, compared to $272.5 million as of December 31, 2020. During the quarter ended March 31, 2021, $98.2 million in net proceeds were received from the sale of 3,622,186 shares of the Company’s common stock pursuant to its at-the-market (ATM) offering.

Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $16.9 million for the quarter ended March 31, 2021, including $0.9 million net sales of MARGENZA, which was launched in mid-March, compared to $13.7 million for the quarter ended March 31, 2020. This increase was primarily due to the recognition of a $10 million milestone from Incyte, partially offset by a decrease of approximately $5.8 million recognized under a clinical supply agreement with Incyte.

R&D Expenses: Research and development expenses were $53.1 million for the quarter ended March 31, 2021, compared to $48.9 million for the quarter ended March 31, 2020. This increase was primarily due to higher expenses related to flotetuzumab, MGC018, MGD019 and preclinical projects, partially offset by a decrease in development and manufacturing costs for retifanlimab.

SG&A Expenses: Selling, general and administrative expenses were $15.0 million for the quarter ended March 31, 2021, compared to $10.2 million for the quarter ended March 31, 2020. This increase was primarily due to MARGENZA pre-launch and launch costs.

Net Loss: Net loss was $51.3 million for the quarter ended March 31, 2021, compared to net loss of $44.7 million for the quarter ended March 31, 2020.

Shares Outstanding: Shares outstanding as of March 31, 2021 were 60,011,206.
Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities as of March 31, 2021, as well as anticipated and potential collaboration payments, should enable it to fund its operations through 2023, assuming the Company’s programs and collaborations advance as currently contemplated.

Conference Call Information

MacroGenics will host a conference call today at 4:30 p.m. (ET) to discuss financial results for the quarter ended March 31, 2021 and provide a corporate update. To participate in the conference call, please dial (877) 303-6253 (domestic) or (973) 409-9610 (international) five minutes prior to the start of the call and provide the Conference ID: 5257004.

The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of the Company’s website at View Source A replay of the webcast will be available shortly after the conclusion of the call and archived on the Company’s website for 30 days following the call.

MACROGENICS, INC.
SELECTED CONSOLIDATED BALANCE SHEET DATA
(Amounts in thousands)

March 31, 2021

December 31, 2020

(unaudited)

Cash, cash equivalents and marketable securities
$
343,177

$
272,531

Total assets
435,445

378,743

Deferred revenue
10,780

11,382

Total stockholders’ equity
350,531

295,884

MACROGENICS, INC.
CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS
(Unaudited)
(Amounts in thousands, except share and per share data)

Three Months Ended March 31,

2021

2020
Revenues:

Revenue from collaborative and other agreements
$
15,184

$
12,967

Product revenue, net
887

Revenue from government agreements
810

715

Total revenues
16,881

13,682

Costs and expenses:

Cost of product sales
17

Research and development
53,121

48,894

Selling, general and administrative
15,036

10,233

Total costs and expenses
68,174

59,127

Loss from operations
(51,293
)

(45,445
)
Other income
21

721

Net loss
(51,272
)

(44,724
)
Other comprehensive income:

Unrealized gain on investments
18

56

Comprehensive loss
$
(51,254
)

$
(44,668
)

Basic and diluted net loss per common share
$
(0.90
)

$
(0.91
)
Basic and diluted weighted average common shares outstanding
57,202,846

49,012,663

Novo Seeds co-leads Adcendo’s EUR 51 Million Series A Financing to Advance Novel Antibody-Drug Conjugates for Treatment of Cancers

On April 29, 2021 Novo Seeds, the early stage investment and company creation team of Novo Holdings, reported an investment in Adcendo, a Danish biotech company which is developing antibody-drug conjugates (ADCs) for the treatment of cancers (Press release, Novo, APR 29, 2021, View Source [SID1234578812]). The EUR 51 million (US$ 62 million) Series A financing was led by Novo Seeds and Ysios Capital, along with RA Capital Management, HealthCap and Gilde Healthcare.

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The new financing, which is the largest Series A financing for a Danish biotech company, will be used to establish a pipeline of ADCs directed at novel cancer targets and to bring the lead program targeting the novel cancer target uPARAP/Endo180 to proof of concept in patients.

The company has been supported by Novo Seeds since 2017 and was incubated in 2018 at the BioInnovation Institute (BII), an international life sciences incubator in Copenhagen. Novo Seeds supported the company amongst others through leveraging its network in industry and academia to recruit world-renowned experts to the company’s Scientific Advisory Board. As part of the financing, Jeroen Bakker, Principal at Novo Seeds, will join the Board.

Commenting on the financing, Henrik Stage, Chief Executive Officer of Adcendo, said: "We are very pleased to welcome world-leading life sciences investor Novo Seeds to our board as a result of today’s financing and in recognition of its involvement in the company since inception. In the last few years, the ADC modality has delivered promising approvals of new drugs as well as significant commercial transactions. We are excited that we have secured this major financing from top tier investors and are looking forward to delivering on our vision of bringing new innovative treatments to cancer patients."

Jeroen Bakker, Principal at Novo Seeds, commented: "One of our ambitions at Novo Seeds is to leverage and nurture the untapped innovation in the Nordic region. We are proud to have been involved with Adcendo since its early days and are very impressed with the progress achieved to date. We are very pleased to now co-lead this investment with such an exceptional syndicate, building on the founders’ early-stage research at The Finsen Laboratory to develop Adcendo into a world leading ADC player, and we look forward to continuing playing a prominent role in shaping the Nordic biotech ecosystem."

uPARAP is a unique novel cancer target overexpressed on the cell surface of several cancers. Being a collagen scavenger receptor that possesses constitutively active and highly efficient internalization and recycling properties, it has been demonstrated to play a role in tumor invasion. The expression and biological mechanisms of uPARAP makes it ideal for an ADC approach as it may be used as a cancer-associated "drug internalization pump" to bring conjugated drugs directly into the cancer cells.

The uPARAP collagen scavenger receptor has been found to be overexpressed by cancer cells in several indications with high unmet needs including soft tissue sarcoma, glioblastoma multiforme, triple-negative breast cancers, leukemia and osteosarcoma, as well as by stromal cells in several high prevalence cancers with substantial stromal tissue content, such as prostate, breast and pancreatic cancer.

In addition to the uPARAP program, Adcendo will build a pipeline of additional novel cancer targets ideally suited to ADC approaches.

Oncolytics Biotech® Announces Upcoming Presentation at the American Society of Clinical Oncology Annual Meeting

On April 29, 2021 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC) reported the acceptance of an abstract discussing its pancreatic adenocarcinoma trial at the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, which is taking place virtually from June 4 – 8, 2021 (Press release, Oncolytics Biotech, APR 29, 2021, View Source [SID1234578794]). Details on the abstract and a corresponding poster presentation are shown below.

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Title: Treatment with pembrolizumab in combination with the oncolytic virus pelareorep promotes anti-tumor immunity in patients with advanced pancreatic adenocarcinoma
Presentation Type: Electronic poster
Session Title: Gastrointestinal Cancer – Gastroesophageal, Pancreatic, and Hepatobiliary
Abstract Number: 4144

The abstract will be published on the ASCO (Free ASCO Whitepaper) Annual Meeting website at 5:00 p.m. ET on May 19, 2021. The corresponding poster will be made available on the meeting website at 9:00 a.m. ET on June 4, 2021.