On December 7, 2020 Paige, a global leader in AI-based digital diagnostics, reported that it will present new data evaluating Paige Breast Alpha, a machine learning system designed to detect breast cancer in digital images of breast tissue, at the upcoming 2020 San Antonio Breast Cancer Symposium (SABCS 2020), taking place virtually December 8-11, 2020 (Press release, Paige AI, DEC 7, 2020, View Source [SID1234572360]).

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For pathologists reviewing breast tissue slides under the microscope, the large volume of slides can pose significant challenges for workload management and pathologist productivity. The poster, "Clinical-grade detection of breast cancer in biopsies and excisions using machine learning," will be featured during a spotlight poster discussion, which highlights some of the most noteworthy and groundbreaking research submitted to the conference.

The poster abstract is available online and viewing details are below:

Clinical-grade detection of breast cancer in biopsies and excisions using machine learning
Authors: Hanna MG, et al.
Session: Spotlight Poster Discussion 6 | Thursday, December 10, 2020 | 3:30pm – 4:45pm CST
Poster #: PD6-03

On December 7, 2020 Ascentage Pharma (6855.HK), a globally focused, clinical-stage biotechnology company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported positive data from two pivotal Phase II clinical trials of HQP1351 (olverembatinib) in an oral presentation at the 62nd ASH (Free ASH Whitepaper) Annual Meeting (Press release, Ascentage Pharma, DEC 7, 2020, View Source [SID1234572378]). These results were presented by the principal investigator of the study, Qian Jiang, MD, Deputy Chief of the Hematology Department at Peking University People’s Hospital. Following oral presentations in 2018 and 2019, this is the third consecutive year in which clinical study results of HQP1351 were selected for oral presentation at the ASH (Free ASH Whitepaper) Annual Meetings, signifying the recognition of HQP1351’s safety and efficacy from the international hematology community.

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HQP1351 is a novel third-generation BCR-ABL tyrosine kinase inhibitor (TKI) developed by Ascentage Pharma for the treatment of patients with CML resistant to first- and second-generation TKIs, including those with the T315I mutation. Based on results from two pivotal Phase II trials, Ascentage Pharma submitted a New Drug Application (NDA) for HQP1351 for the treatment of patients with T315I-mutated CML in chronic-phase (CML-CP) or accelerated-phase (CML-AP) in China this year, and the NDA was subsequently granted Priority Review status.

At 12:30 PST, December 7, during the session "Chronic Myeloid Leukemia: Therapy: CML: New and Beyond", Dr. Qian Jiang delivered an oral presentation on results from the pivotal Phase II studies of HQP1351, in an address titled "Novel BCR-ABL1 Tyrosine Kinase Inhibitor (TKI) HQP1351 (Olverembatinib) Is Efficacious and Well Tolerated in Patients with T315I-Mutated Chronic Myeloid Leukemia (CML): Results of Pivotal (Phase II) Trials".

Highlights of the results:

Two pivotal Phase II trials of HQP1351 in patients with TKI-resistant and T315I-mutated CML-CP or CML-AP were conducted in China. Patients in the studies were administered HQP1351 at 40 mg once every other day (QOD).
As of the data cut-off date of March 23, 2020, pivotal Phase II study HQP1351-CC201 had enrolled 41 patients with CML-CP. Across a median follow-up of 7.9 months, the mean 3-month progression-free survival (PFS) was 100%, and the 6-month PFS was 96.7%. A total of 75.6% of evaluable patients achieved a major cytogenetic response (MCyR), including 65.9% with a complete cytogenetic response (CCyR) and 48.8% with a major molecular response (MMR).
As of the data cut-off date of February 11, 2020, pivotal Phase II study HQP1351-CC202 had enrolled 23 patients with CML-AP. Across a median follow-up of 8.2 months, the 3-month PFS was 100% and the 6-month PFS was 95.5%. A total of 78.3% of evaluable patients achieved a major hematologic response (MaHR), including 60.9% of patients with a complete hematologic response (CHR). A further 52.2% of patients achieved MCyR, including 39.1% with CCyR and 26.1% with MMR.
In study HQP1351-CC201, the most frequent treatment-related adverse event (TRAE) of Grade 3-4 was thrombocytopenia (48.8%), and there were no treatment-related deaths.
In study HQP1351-CC202, the most frequent TRAE of Grade 3-4 was also thrombocytopenia (52.2%).
Results from the two studies show that HQP1351 was efficacious and well tolerated in patients with T315I-mutated and TKI-resistant CML-AP or CML-CP, and the probability and depth of clinical response is expected to increase with prolonged treatment period.
"Once T315I mutation occurs in patients with CML-CP or CML-AP, first- and second-generation TKIs are no longer effective. Currently, there is no approved treatment for these TKI-resistant patients in China, thus representing an urgent unmet medical need," said presenting author Dr. Qian Jiang. "Results from these two pivotal Phase II studies of HQP1351 in patients with T315I-mutated and TKI-resistant CML-AP or CML-CP have demonstrated promising efficacy and tolerability profiles. We remain steadfast to continuing the clinical development of this China-developed innovative therapy and bringing it to patients as early as possible."

"We are very pleased that results from the Phase II studies of HQP1351, a third-generation BCR-ABL inhibitor, have demonstrated encouraging efficacy and tolerability," said Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma. "For this drug candidate to be selected for oral presentation at the ASH (Free ASH Whitepaper) annual meeting in three consecutive years really shows the recognition of HQP1351 as a potential treatment for CML from the international hematology community. The release of these results marks another major milestone for the development of HQP1351, following the NDA submission and Priority Review designation in China. We hope HQP1351 will soon obtain its market authorizations so that patients with drug-resistant CML in China and around the world may start benefiting from this novel therapy."

About HQP1351 (Olverembatinib)

Being developed by Ascentage Pharma, HQP1351 is a novel, orally active, potent third-generation BCR-ABL tyrosine kinase inhibitor (TKI) designed to effectively target a spectrum of BCR-ABL mutants, including T315I, and the first China-developed third-generation BCR-ABL TKI targeting drug-resistant chronic myeloid leukemia (CML). At present, a New Drug Application (NDA) for HQP1351 has been submitted in China, and the application was subsequently granted the Priority Review status. In July 2019, HQP1351 was cleared by the US Food and Drug Administration (FDA) to enter a Phase Ib clinical study. In May 2020, the drug candidate was granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA. Furthermore, a Phase Ib trial of HQP1351 in patients with gastrointestinal stromal tumor (GIST) is also ongoing in China.

On December 7, 2020 GENFIT (Nasdaq and Euronext: GNFT), a late-stage biopharmaceutical company dedicated to improving the lives of patients with metabolic and chronic liver diseases, reported that it has signed bond repurchase agreements with holders of its convertible bonds maturing in October 2022 (the "OCEANEs") (Press release, Genfit, DEC 7, 2020, https://ir.genfit.com/news-releases/news-release-details/genfit-announces-successful-completion-key-milestone-partial [SID1234572281]).

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Pascal Prigent, CEO of GENFIT, commented: "We are delighted to have reached this key milestone, and would like to thank the OCEANE holders who supported the Company’s buyback proposal for the significant efforts they have made to support the company’s future evolution. The restructuring of the OCEANEs is an important step in the execution of our corporate strategy and I am confident that our shareholders and OCEANE holders will now vote in favor of this transaction. Indeed, it will enable us to operationally and financially implement our strategic plan focused on the development of elafibranor in ELATIVE, our Phase 3 PBC trial, as well as further expand our NIS4 technology for NASH diagnosis. The current deal structure essentially cuts our debt in half and pushes its maturity to Q4 2025, which should give us ample opportunity to maximize the commercial potential of our assets and create significant value for bond holders and shareholders alike."

Final results of the partial buyback, and amendments of the existing terms and conditions of the OCEANEs

Following competition of the fixed-price reverse bookbuilding process begun on November 23, the Company has signed bond repurchase agreements with OCEANEs holders to buyback a total of 2,895,260 OCEANEs at a price of €16.40 per OCEANE, representing a total repurchase price of 47.48 million euros.

The repurchased OCEANEs represent 47.6% out of the 6,081,081 outstanding OCEANEs and 85,699,696 euros in nominal amount.

Following the cancellation of the OCEANEs that will be repurchased in the partial buyback, 3,185,821 OCEANEs would remain outstanding, representing a residual nominal amount of 94,300,301.6 euros.

The settlement of the OCEANEs buyback remains contingent on – and will occur after – the approval by GENFIT shareholders and OCEANEs holders of the following adjustments to the terms:

New maturity date of October 16, 2025;
Increase of the conversion ratio from 1:1 to 1:5.5, resulting in an implied conversion price of €5.38 per share;
Deferral of the initiation of the early redemption period1 in the OCEANEs terms and conditions (initiating on November 3, 2023); and
Amendment of the ratchet clause, adjusting the conversion ratio in the event of a tender offer targeting GENFIT shares, to incorporate the extension of the OCEANEs maturity date until 2025. The adjustment would be calculated from the date of approval by the OCEANEs holders of the amended terms and conditions (i.e. the date on which the OCEANEs holders meeting would be held) until the new maturity date (i.e. October 16, 2025).

(The "OCEANEs Amendments")

The nominal value and redemption price of the OCEANEs will remain unchanged at €29.60 per OCEANE. The existing terms and conditions of the OCEANEs not mentioned above will remain unchanged.

In order to obtain approval of the OCEANEs Amendments, the Company will convene a general meeting of its shareholders on January 13, 2021. Should the quorum not be achieved, a second shareholders meeting will be convened on January 25, 2021, in addition to an OCEANEs bondholder general meeting on January 25, 2021.

The buyback price of €16.40 includes the accrued interest for the period since the latest interest payment date, on October 16, 2020, until the buyback settlement date, expected to be January 29 2021, at the latest. For illustrative purposes, should an effective buyback date occur on January 29, 2021, the buyback price per bond (excluding accrued interests) would be €16.10, and the accrued interest amount would be €0.30. A change in the buyback settlement date (either earlier or later) will not lead to any change of the buyback price2.

Should the new conversion ratio be accepted, the implied conversion price (nominal amount of €29.60 divided by the 1:5.5 conversion ratio) would be €5.38 per bond. This represents a conversion premium3 of 18.8% compared to the closing share price on December 4, 2020 (€4.53), and a 32.2% premium compared to the volume weighted average price between November 16 and November 20, 2020 (i.e. the five trading days prior to the announcement of the final terms of the transaction on November 23, 2020)4.

Based on the new conversion ratio, 17,522,016 new shares could be issued upon conversion5 of all OCEANEs remaining post-buy-back, representing 45.1% of the current share capital of the Company (versus 15.6% with the current conversion ratio). In the event of a full conversion of the OCEANEs at maturity, the OCEANEs holders would own 31.08% of the share capital of the Company, and 30.8% should all the outstanding stock options and share warrants (BSA) be exercised, and all the outstanding free shares vest (based on instruments outstanding as of December 31, 2019).

Independent Expert and Prospectus

Following recommendation of a committee composed of a majority of independent directors, the Company’s Board of Directors has appointed an independent expert to review the balance of the terms of the transaction between the shareholders and OCEANE holders. This has been done on a voluntary basis and the report will be made publicly available.

As a result of the new conversion ratio, in the event of a full conversion of the OCEANEs outstanding post-buyback, the number of shares that would potentially be issued, would be higher than 20% of the share capital6 and the Company will file with the French Autorité des Marchés Financiers (AMF) a listing prospectus composed of the Company’s 2019 Universal Registration Document filed with the AMF on May 27, 2020 under number D.20-0503, an amendment of this Universal Registration Document, a securities note (note d’opération) and a summary of the prospectus, for approval by the end of December 2020.

Additional information relating to the convening of the shareholders’ extraordinary general meeting

Due to the ongoing lockdown and prohibition on public gatherings currently imposed by the French government to prevent the spread of Covid-19, the Board of Directors of the Company decided that the extraordinary shareholders’ meeting will be held behind closed doors, that is to say without the presence of shareholders and other persons who are usually entitled to attend, in accordance with the provisions of article 4 of Ordinance no. 2020-321 of March 25, 2020 adapting the rules for meeting and deliberation of meetings and governing bodies of legal persons and entities without legal personality of private law due to the Covid-19 epidemic, which application period has been extended and terms have been modified by the Ordinance no. 2020-1497 of December 2, 2020.

The convening notice published in the French legal announcements bulletin (Bulletin des Annonces Légales Obligatoires) and made available in the Investors & Media section of the Company’s website (https://ir.genfit.com/financial-information/shareholders-meeting) outlines the procedures by which shareholders may participate in the shareholders’ extraordinary general meeting, notwithstanding the exceptional measures required in order to comply with regulatory constraints and ensure the health and safety of our shareholders.

Shareholders may provide their voting instructions via the Internet through the VOTACCESS platform. A tutorial to familiarize shareholders with this online voting platform will be available in the same section of the website, as well as a toll-free number (France only: 0800 94 06 51) to call with any questions regarding how to participate to the shareholders’ extraordinary general meeting.

In accordance with Article 3 of Ordinance no. 2020-1497 of December 2, 2020, the Company will broadcast the shareholders’ extraordinary general meeting live except if technical reasons make it impossible or severely trouble such broadcast. The Company will also ensure a replay of such broadcast. Every written question asked by shareholders, together with the answers given in accordance with the third and fourth paragraphs of Article L. 225-108 of the French Code de commerce, will be published in the dedicated section of the Company’s website provided for in the fourth paragraph of such article.

Documentation regarding the shareholders’ extraordinary general meeting will be made available to shareholders in accordance with existing regulations on the Company’s website, in the Investors & Media section (https://ir.genfit.com/financial-information/shareholders-meeting).

Further details on the convening of the OCEANEs holders’ meeting to be held on January 25, 2020 will be made available later on.

Anticipated Calendar of Events

December 7, 2020 Publication of the convening notice (avis de reunion valant convocation) of the shareholders’ extraordinary general meeting
December 16, 2020 Publication of the meeting notice (avis de réunion) of the OCEANEs holders’ general meeting
Before end of December 2020 Submission of the amendment to the Universal Registration Document and approval of the prospectus by the AMF
Publication of the prospectus
January 13, 2021 Shareholders’ extraordinary general meeting upon first convocation
Press release announcing the results of the shareholders’ extraordinary general meeting or, due to the required quorum not being reached, second convening notice (avis de convocation) of the shareholders extraordinary general meeting
January 25, 2021 Shareholders’ extraordinary general meeting upon second convocation
OCEANEs holders’ general meeting
January 27, 2021 Decision of Chief Executive Officer authorising the OCEANEs Amendments
January 29, 2021
(at the latest) OCEANEs partial buyback settlement date

On December 7, 2020 MorphoSys AG (FSE: MOR; Prime Standard Segment; MDAX & TecDAX; NASDAQ:MOR) and Incyte (Nasdaq:INCY) reported that preliminary data from firstMIND, the ongoing Phase 1b, open-label, randomized study on the safety and efficacy of tafasitamab or tafasitamab plus lenalidomide in addition to R-CHOP for patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) were presented today during the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition (ASH) (Free ASH Whitepaper) (Press release, MorphoSys, DEC 7, 2020, View Source [SID1234572329]). Additionally, a long-term subgroup analysis of the L-MIND study investigating tafasitamab combined with lenalidomide in patients with relapsed or refractory DLBCL was also presented at ASH (Free ASH Whitepaper).

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The preliminary results of firstMIND indicate that tafasitamab plus lenalidomide in addition to R-CHOP shows an acceptable tolerability profile. Toxicities appear to be similar to what is expected with R-CHOP alone or in combination with lenalidomide. Serious or severe neutropenia and thrombocytopenia events (grade 3 or higher) were more frequent in the tafasitamab plus lenalidomide arm. The incidence of febrile neutropenia was comparable between both arms and the average relative dose intensity of R-CHOP was maintained in both arms. Interim response assessments after three cycles were available for 45 patients. In both arms combined, 41/45 (91.1%) of patients had an objective response as per Lugano 2014.1

The preliminary data from this ongoing study in first-line DLBCL warrant further investigation. To that end, MorphoSys and Incyte plan to initiate frontMIND, a Phase 3 trial evaluating tafasitamab plus lenalidomide in combination with R-CHOP compared to R-CHOP alone as first-line treatment for patients with newly diagnosed DLBCL.

"The preliminary firstMIND study results mark another important step as we explore the potential of tafasitamab as a backbone therapy," said Dr. Malte Peters, Chief Research and Development Officer at MorphoSys. "Given the data available to date, including data from the L-MIND study, we believe that the mechanism of action, efficacy and safety profile of tafasitamab have the potential to make it a preferred combination partner as we seek to transform the standard of care in DLBCL. We are committed to developing innovative therapies to battle this aggressive disease for the benefit of patients with DLBCL, and look forward to beginning the planned frontMIND in the first half of 2021."

"The initial results of the firstMIND study, shared today at ASH (Free ASH Whitepaper), as well as the long-term analyses from L-MIND, underscore the potential of tafasitamab as a combination therapeutic for patients with DLBCL, where there remains a significant unmet need. Along with our partners at MorphoSys, we are pleased to be moving forward with the initiation of a Phase 3 study in 2021," said Steven Stein, M.D., Chief Medical Officer at Incyte.

In addition to the firstMIND data presented today, the long-term L-MIND analyses showed that treatment with tafasitamab plus lenalidomide resulted in durable responses after >=2 years of follow-up. At the time of analysis, patients with complete responses (CR) continued to experience durable treatment responses, including long duration of response (DoR) and overall survival (OS). The data also showed that tafasitamab plus lenalidomide taken for 12 cycles, followed by tafasitamab until progression, did not result in any unexpected safety signals.2

In July 2020, the FDA approved Monjuvi(R) (tafasitamab-cxix), a humanized Fc-modified cytolytic CD19-targeting monoclonal antibody, in combination with lenalidomide for the treatment of adult patients with relapsed or refractory DLBCL not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).3

The FDA decision represented the first approval of a second-line treatment for adult patients with DLBCL who progressed during or after first-line therapy.

About Diffuse Large B-cell Lymphoma (DLBCL)
DLBCL is the most common type of non-Hodgkin lymphoma in adults worldwide4, characterized by rapidly growing masses of malignant B-cells in the lymph nodes, spleen, liver, bone marrow or other organs. It is an aggressive disease with about one in three patients not responding to initial therapy or relapsing thereafter5. In the United States each year, approximately 10,000 patients are diagnosed with relapsed or refractory DLBCL who are not eligible for autologous stem cell transplant (ASCT).6,7,8

About firstMIND
The firstMIND (NCT04134936) trial is a Phase 1b, randomized study of tafasitamab + R-CHOP (Arm A) or tafasitamab + lenalidomide + R-CHOP (Arm B) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The study includes a safety run-in phase and a main phase. In the safety run-in phase, 24 patients were enrolled. The primary objective is to assess safety; secondary objectives include objective response rate, PET negative complete response (PET-CR) rate at end of treatment, progression-free survival, event-free survival, long-term safety, pharmacokinetics and immunogenicity of tafasitamab.

About Tafasitamab
Tafasitamab is a humanized Fc-modified cytolytic CD19 targeting monoclonal antibody. In 2010, MorphoSys licensed exclusive worldwide rights to develop and commercialize tafasitamab from Xencor, Inc. Tafasitamab incorporates an XmAb(R) engineered Fc domain, which mediates B-cell lysis through apoptosis and immune effector mechanism including antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP).

Monjuvi(R) (tafasitamab-cxix) is approved by the U.S. Food and Drug Administration in combination with lenalidomide for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) not otherwise specified, including DLBCL arising from low grade lymphoma, and who are not eligible for autologous stem cell transplant (ASCT). This indication is approved under accelerated approval based on overall response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

In January 2020, MorphoSys and Incyte entered into a collaboration and licensing agreement to further develop and commercialize tafasitamab globally. Monjuvi(R) is being co-commercialized by Incyte and MorphoSys in the United States. Incyte has exclusive commercialization rights outside the United States.

A marketing authorization application (MAA) seeking the approval of tafasitamab in combination with lenalidomide in the EU has been validated by the European Medicines Agency (EMA) and is currently under review for the treatment of adult patients with relapsed or refractory DLBCL, including DLBCL arising from low grade lymphoma, who are not candidates for ASCT.

Tafasitamab is being clinically investigated as a therapeutic option in B-cell malignancies in a number of ongoing combination trials.

Monjuvi(R) is a registered trademark of MorphoSys AG.
XmAb(R) is a registered trademark of Xencor, Inc.

Important Safety Information
What are the possible side effects of MONJUVI?
MONJUVI may cause serious side effects, including:

– Infusion reactions. Your healthcare provider will monitor you for infusion reactions during your infusion of MONJUVI. Tell your healthcare provider right away if you get chills, flushing, headache, or shortness of breath during an infusion of MONJUVI.

– Low blood cell counts (platelets, red blood cells, and white blood cells). Low blood cell counts are common with MONJUVI, but can also be serious or severe. Your healthcare provider will monitor your blood counts during treatment with MONJUVI. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or any bruising or bleeding.

– Infections. Serious infections, including infections that can cause death, have happened in people during treatments with MONJUVI and after the last dose. Tell your healthcare provider right away if you get a fever of 100.4 F (38 C) or above, or develop any signs and symptoms of an infection.

The most common side effects of MONJUVI include:

– Feeling tired or weak

– Diarrhea

– Cough

– Fever

– Swelling of lower legs or hands

– Respiratory tract infection

– Decreased appetite

These are not all the possible side effects of MONJUVI.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Before you receive MONJUVI, tell your healthcare provider about all your medical conditions, including if you:

– Have an active infection or have had one recently.

– Are pregnant or plan to become pregnant. MONJUVI may harm your unborn baby. You should not become pregnant during treatment with MONJUVI. Do not receive treatment with MONJUVI in combination with lenalidomide if you are pregnant because lenalidomide can cause birth defects and death of your unborn baby.

– You should use an effective method of birth control (contraception) during treatment and for at least 3 months after your final dose of MONJUVI.

– Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with MONJUVI.

– Are breastfeeding or plan to breastfeed. It is not known if MONJUVI passes into your breastmilk. Do not breastfeed during treatment for at least 3 months after your last dose of MONJUVI.

You should also read the lenalidomide Medication Guide for important information about pregnancy, contraception, and blood and sperm donation.

Tell your healthcare provider about all the medications you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

On December 7, 2020 MacroGenics, Inc. (NASDAQ: MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, reported updated results from a dose expansion study of tebotelimab, an investigational, bispecific PD-1 × LAG-3 DART molecule, in patients with diffuse large B-cell lymphoma (DLBCL) (Press release, MacroGenics, DEC 7, 2020, View Source [SID1234572345]). The data were presented at the 62nd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) taking place December 5-8, 2020.

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LAG-3 has been shown to be highly expressed in DLBCL and has emerged as a therapeutic target of interest in this population, while PD-1-targeted therapy has yielded modest efficacy. There remains significant unmet need for patients with relapsed/refractory (R/R) DLBCL.

In one of the tebotelimab monotherapy dose expansion cohorts, 20 DLBCL patients were enrolled, half of whom were CAR T cell therapy experienced. As of the October 23, 2020 data cut-off, there were 13 response-evaluable patients.

A preliminary objective response rate (ORR) of 53.8% (7 of 13 patients) was observed, including responses in five of seven CAR T cell-naïve patients and in two of six CAR T cell experienced patients, the latter of whom both had complete responses. A preliminary duration of response of up to 168 days was observed, with six of seven ongoing responses as of the cut-off date. In the study, baseline LAG-3 expression appeared to associate with clinical response, with additional analyses ongoing.

Tebotelimab was generally well-tolerated among heavily pre-treated R/R DLBCL patients, with manageable infusion-related reactions and no evidence of tumor lysis syndrome. The most common TRAE was pyrexia, which occurred in three (15%) patients. A single Grade 3 TRAE of anemia was observed.

"Although early, the preliminary ORR observed in relapsed/refractory DLBCL patients treated with tebotelimab is promising," said Scott Koenig, M.D., Ph.D., President and Chief Executive Officer of MacroGenics. "Beyond our continued enrollment of patients in the combination study of tebotelimab in solid tumors, we look forward to presenting data from the full cohort of the 20 enrolled DLBCL patients, as well as potentially defining a future registration path for this DART molecule."

About Diffuse Large B-Cell Lymphoma

DLBCL is the most common histologic subtype of non-Hodgkin lymphoma (NHL) accounting for approximately 25 percent of NHL cases globally. According to published research, the incidence in the U.S. and England is approximately 7 cases per 100,000 persons per year, with a median age at presentation of 64 years. DLBCL represents a heterogeneous group of tumors consisting of large, transformed B cells with prominent nucleoli and basophilic cytoplasm, a diffuse growth pattern, and a high proliferation fraction. While DLBCL is curable in approximately half of cases with current therapy, particularly those who achieve a complete remission with first-line treatment, significant unmet medical need remains for patients with relapsed or refractory disease.

About Tebotelimab

Tebotelimab (previously known as MGD013) is an investigational, first-in-class bispecific, tetravalent DART molecule targeting PD-1 and LAG-3. Tebotelimab has been engineered to concomitantly or independently bind to PD-1 and LAG-3 and disrupt these non-redundant inhibitory pathways to further restore exhausted T-cell function. Tebotelimab is being evaluated in a Phase 1 dose expansion study as monotherapy in several tumor types, including both solid tumors and hematological malignancies, and in combination with margetuximab, an investigational Fc-engineered monoclonal antibody targeting HER-2, in three cohorts of patients with advanced HER2-positive cancers (NCT03219268). Tebotelimab will also be evaluated in combination with margetuximab and chemotherapy as part of the ongoing Phase 2/3 MAHOGANY study in patients with HER2-positive gastric or gastroesophageal junction cancer (NCT04082364). MacroGenics’ regional partner in Greater China, Zai Lab, participates in the MAHOGANY study and is also evaluating tebotelimab independently in Phase 1 combination studies with niraparib, a PARP inhibitor, and brivanib, a dual target tyrosine kinase inhibitor of the VEGF and FGF receptors, for the study of advanced gastric cancer and hepatocellular carcinoma, respectively.