On April 23, 2021 AbbVie (NYSE: ABBV) reported that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion for VENCLYXTO (venetoclax) in combination with hypomethylating agents for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy (Press release, AbbVie, APR 23, 2021, View Source [SID1234578398]). The positive CHMP opinion is a scientific recommendation for marketing authorization to the European Commission (EC), which is expected to deliver its final decision on VENCLYXTO combination therapy for use in AML in the first half of 2021.

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The positive CHMP opinion represents the third for an extension of indications for VENCLYXTO. The opinion is based on results from the double-blind, placebo-controlled VIALE-A (M15-656) and the Phase 1b open-label, nonrandomized, multicenter M14-358 trial.

"This positive CHMP opinion for VENCLYXTO in acute myeloid leukemia is a critical step to providing new therapeutic options in the European Union for patients with this devastating disease," said Mohamed Zaki, M.D., Ph.D., vice president and global head of oncology development at AbbVie. "Enabling improved outcomes including potentially prolonging the lives of patients with malignant diseases such as acute myeloid leukemia is part of our mission and an objective we pursue relentlessly every day."

AML is the most common acute leukemia in the world.1 An estimated 160,000 people are currently living with the disease globally. 1 The rate of new cases of acute myeloid leukemia is 4.3 per 100,000 men and women per year.3 It is also among the most difficult blood cancers to treat.2 Despite advances in available therapies and care, the five-year survival rate for patients diagnosed with AML remains approximately 29 percent.3 AML typically worsens quickly, and due to age and comorbidities, not all patients can tolerate intensive chemotherapy.4

"AML is an incredibly aggressive form of cancer, and patients who are diagnosed with this disease are often so ill that they cannot tolerate the intensive chemotherapy that healthcare providers would typically prescribe," said Hartmut Döhner, M.D., Professor of Medicine and Director, Department of Hematology, Oncology, Palliative Care, Rheumatology and Infectious Diseases at University Hospital in Ulm, Germany. "VENCLYXTO combination therapy is a promising advancement for patients and their healthcare providers facing this challenging, lethal form of cancer."

Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S.

About the VENCLYXTO AML Clinical Trial Program
AbbVie’s clinical trial program to evaluate VENCLYXTO combination therapy in patients with newly diagnosed acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy included two studies conducted around the world.

VIALE-A (M15-656) Phase 3 Trial
The randomized, double-blind, placebo-controlled VIALE-A (M15-656) trial evaluated the efficacy and safety of VENCLYXTO in combination with azacitidine in patients with newly diagnosed AML who were ineligible for intensive chemotherapy. The study met its primary endpoints of statistically significant improvement of overall survival (OS) and complete remission rate and complete remission with incomplete hematologic recovery (CR + CRi). OS was 14.7 months for the VENCLYXTO plus azacitidine arm versus 9.6 months in the placebo plus azacitidine arm. The study also met secondary endpoints, with the VENCLYXTO plus azacitidine arm resulting in a CR rate of 36.7 percent vs. 17.9 percent in the placebo plus azacitidine arm and a composite complete remission rate (CR + CRi) of 66.4 percent versus 28.3 percent. The safety profile of VENCLYXTO plus azacitidine was consistent with the known side-effect profiles of both agents, and adverse events (AEs) were consistent with expectations for an older AML population; no differences between the two treatment arms with respect to quality-of-life measures were seen. The most frequently reported serious AEs in the VENCLYXTO plus azacitidine arm and placebo plus azacitidine arm were febrile neutropenia (in 30 percent and 10 percent), pneumonia (in 17 percent and 22 percent), sepsis (in 6 percent and 8 percent), and haemorrhage (in 9 percent and 6 percent).5

M14-358 Phase 1b Trial
The non-randomized, open-label M14-358 trial evaluated VENCLYXTO in combination with azacitidine or decitabine in patients with newly diagnosed AML. The trial showed patients treated with VENCLYXTO in combination with azacitidine achieved a CR rate of 44 percent and a CR+CRi rate of 71 percent. The median duration of response for patients treated with VENCLYXTO in combination with azacitidine who achieve a CR or CRi was 21.9 months. Median time to first CR or CRi was 1.2 months (range: 0.7 to 7.7 months). Patients who received VENCLYXTO in combination with decitabine achieved a CR rate of 55 percent and a CR+CRi rate of 74 percent. The median duration of response for patients treated with VENCLYXTO in combination with decitabine who achieved a CR or CRi was 15 months. Median time to first CR or CRi was 1.9 months (range: 0.9 to 5.4 months). The most frequently reported serious AEs in patients receiving VENCLYXTO in combination with azacitidine were febrile neutropenia (31 percent) and pneumonia (26 percent). The most frequently reported serious AEs in patients receiving VENCLYXTO in combination with decitabine were febrile neutropenia (42 percent), pneumonia (29 percent), bacteraemia (16 percent) and sepsis (6 percent).6

About VENCLYXTO (venetoclax)

VENCLYXTO (venetoclax) is a first-in-class medicine that selectively binds and inhibits the B-cell lymphoma-2 (BCL-2) protein. In some blood cancers, BCL-2 prevents cancer cells from undergoing their natural death or self-destruction process, called apoptosis. VENCLYXTO targets the BCL-2 protein and works to help restore the process of apoptosis.

VENCLYXTO is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the U.S. and by AbbVie outside of the U.S. Together, the companies are committed to BCL-2 research and to studying venetoclax in clinical trials across several blood and other cancers. Venetoclax is approved in more than 80 countries, including the U.S.

Indication and Important VENCLYXTO (venetoclax) EU Safety Information7

Indication

Venclyxto in combination with obinutuzumab is indicated for the treatment of adult patients with previously untreated chronic lymphocytic leukaemia (CLL).

Venclyxto in combination with rituximab is indicated for the treatment of adult patients with CLL who have received at least one prior therapy.

Venclyxto monotherapy is indicated for the treatment of CLL:

In the presence of 17p deletion or TP53 mutation in adult patients who are unsuitable for or have failed a B-cell receptor pathway inhibitor, or
In the absence of 17p deletion or TP53 mutation in adult patients who have failed both chemoimmunotherapy and a B-cell receptor pathway inhibitor.
Contraindications

Hypersensitivity to the active substance or to any of the excipients is contraindicated. Concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase due to increased risk for tumor lysis syndrome (TLS). Concomitant use of preparations containing St. John’s wort as VENCLYXTO efficacy may be reduced.

Special Warnings & Precautions for Use

TLS, including fatal events, has occurred in patients with CLL when treated with VENCLYXTO.

Patients should be assessed for risk and should receive appropriate prophylaxis, monitoring, and management for TLS. The risk of TLS is a continuum based on multiple factors, including comorbidities. VENCLYXTO poses a risk for TLS in the initial 5-week dose-titration phase. Changes in electrolytes consistent with TLS that require prompt management can occur as early as 6 to 8 hours following the first dose of VENCLYXTO and at each dose increase.

Neutropenia (grade 3 or 4) has been reported and complete blood counts should be monitored throughout the treatment period.

Serious infections including sepsis with fatal outcome have been reported. Monitoring of any signs and symptoms of infection is required. Suspected infections should receive prompt treatment including antimicrobials and dose interruption or reduction as appropriate.

Live vaccines should not be administered during treatment or thereafter until B-cell recovery.

Drug Interactions

CYP3A inhibitors may increase VENCLYXTO plasma concentrations. At initiation and dose-titration phase: Strong CYP3A inhibitors are contraindicated due to increased risk for TLS and moderate CYP3A inhibitors should be avoided. If moderate CYP3A inhibitors must be used, physicians should refer to the SmPC for dose adjustment recommendations. At steady daily dose: moderate or strong CYP3A inhibitors must be used, physicians should refer to the VENCLYXTO summary of product characteristics (SmPC) for dose adjustment recommendations.

Avoid concomitant use of P-gp and BCRP inhibitors at initiation and during the dose titration phase.

CYP3A4 inducers may decrease VENCLYXTO plasma concentrations. Avoid coadministration with strong or moderate CYP3A inducers. These agents may decrease venetoclax plasma concentrations.

Co-administration of bile acid sequestrants with VENCLYXTO is not recommended as this may reduce the absorption of VENCLYXTO.

Adverse Reactions

The most commonly occurring adverse reactions (>=20%) of any grade in patients receiving venetoclax in the combination studies with obinutuzumab or rituximab were neutropenia, diarrhoea, and upper respiratory tract infection. In the monotherapy studies, the most common adverse reactions were neutropenia/neutrophil count decreased, diarrhoea, nausea, anaemia, fatigue, and upper respiratory tract infection.

The most frequently occurring serious adverse reactions (>=2%) in patients receiving venetoclax in combination with obinutuzumab or rituximab were pneumonia, sepsis, febrile neutropenia, and TLS. In the monotherapy studies, the most frequently reported serious adverse reactions (>=2%) were pneumonia and febrile neutropenia.

Discontinuations due to adverse reactions occurred in 16% of patients treated with venetoclax in combination with obinutuzumab or rituximab in the CLL14 and Murano studies, respectively. In the monotherapy studies with venetoclax, 11% of patients discontinued due to adverse reactions.

Dosage reductions due to adverse reactions occurred in 21% of patients treated with the combination of venetoclax and obinutuzumab in CLL14, in 15% of patients treated with the combination of venetoclax and rituximab in Murano, and in 14% of patients treated with venetoclax in the monotherapy studies. The most common adverse reaction that led to dose interruptions was neutropenia.

Specific Populations

Patients with reduced renal function (CrCl <80 mL/min) may require more intensive prophylaxis and monitoring to reduce the risk of TLS at initiation and during the dose-titration phase. Safety in patients with severe renal impairment (CrCl <30 mL/min) or on dialysis has not been established, and a recommended dose for these patients has not been determined.

For patients with severe (Child-Pugh C) hepatic impairment, a dose reduction of at least 50% throughout treatment is recommended.

VENCLYXTO may cause embryo-fetal harm when administered to a pregnant woman. Advise nursing women to discontinue breastfeeding during treatment.

This is not a complete summary of all safety information. See VENCLYXTO (venetoclax) SmPC at www.ema.europa.eu. Globally, prescribing information varies; refer to the individual country product label for complete information.

About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for multiple blood cancers while advancing a dynamic pipeline of investigational therapies across a range of cancer types. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potentially breakthrough medicines. We are evaluating more than 20 investigational medicines in over 300 clinical trials across some of the world’s most widespread and debilitating cancers. As we work to have a remarkable impact on people’s lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit View Source

On April 23, 2021 Zai Lab Limited ("Zai Lab" or the "Company") (NASDAQ:ZLAB, HKEX: 9688), an innovative commercial stage biopharmaceutical company, reported the closing of its previously announced underwritten public offering of 4,776,000 American depositary shares ("ADSs"), each representing one ordinary share of the Company, at a price of US$150.00 per ADS (the "ADS Offering") (Press release, Zai Laboratory, APR 23, 2021, View Source [SID1234578395]). Zai Lab had also granted the underwriters a 30-day option to purchase up to an additional 716,400 ADSs at the public offering price, less underwriting discounts and commissions. The underwriters fully exercised their option to purchase these additional ADSs. The ADS Offering closed on April 23, 2021.

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The expected total global offering gross proceeds to Zai Lab, including both the ADS Offering and the previously announced underwritten offering of 224,000 ordinary shares (the "Ordinary Shares Offering), are approximately US$857.5 million.

The gross proceeds to Zai Lab from the ADS Offering, before deducting underwriting discounts and commissions and other offering expenses, were approximately US$823.9 million.

The closing of the Ordinary Shares Offering is expected on or about April 28, 2021, and will be settled in Hong Kong dollars at a price of HK$1,164.20 per ordinary share.

J.P. Morgan Securities LLC, Goldman Sachs & Co. LLC, Jefferies LLC, Citigroup Global Markets Inc., SVB Leerink LLC and Guggenheim
Securities, LLC acted as joint book-running managers for the ADS offering.

The ADSs were offered pursuant to a shelf registration statement on Form S-3ASR, which became automatically effective upon filing with the U.S. Securities and Exchange Commission ("SEC") on April 19, 2021.

The ADS Offering was made only by means of a prospectus supplement and an accompanying prospectus included in Form-S-3ASR. The registration statement on Form S-3ASR and the prospectus supplement are available at the SEC’s website at: View Source Copies of the prospectus supplement and the accompanying prospectus may be obtained from: (i) J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, via telephone at 1-866-803-9204 or via email at [email protected], (ii) Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, facsimile: 212-902-9316 or by emailing [email protected], (iii) Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York 10022, or by telephone at 1-877-821-7388 or via email at [email protected], (iv) Citigroup Capital Markets Inc., c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, NY 11717 or by telephone at 1-800-831-9146 and (v) SVB Leerink LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at 1-800-808-7525 ex. 6105 or by email at [email protected].

This press release does not constitute an offer to sell or the solicitation of an offer to buy ADSs, ordinary shares or any other securities, nor shall there be any sale of ADSs or ordinary shares in any state or jurisdiction in which such an offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On April 23, 2021 iCo Therapeutics Inc. ("iCo" or the "Company") (TSXV: iCo) (OTCQB: iCoTF) reported that, in connection with its proposed business combination with Satellos Bioscience Inc. ("Satellos") by way of a plan of arrangement (the "Arrangement"), as previously announced on March 22, 2021, it intends to offer on a private placement basis (the "Financing") 85,294,117 subscription receipts (the "Subscription Receipts") at a price of $0.085 per Subscription Receipt for aggregate gross proceeds of approximately C$7.25 million, representing an upsize from the C$6 million financing announced on March 22, 2021 (Press release, iCo Therapeutics, APR 23, 2021, View Source [SID1234578391]). Each Subscription Receipt will entitle the holder thereof to receive, upon satisfaction of certain escrow release conditions, and without payment of additional consideration, one common share in the Resulting Issuer (as described below). The proceeds from the Financing are to be placed in escrow and, upon satisfaction of the release conditions and completion of the Arrangement, will be used for research, development, and general corporate expenses of the Resulting Issuer.

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The common shares underlying the Subscription Receipts are subject to a lock-up agreement and the Subscription Receipts and the underlying common shares of the Resulting Issuer will be subject to a hold period expiring 4 months and one day from the date of issuance in accordance with applicable Canadian securities laws. The Financing is anticipated to close on or about April 27, 2021, subject to approval by the TSX Venture Exchange (the "Exchange").

The Financing is led by Bloom Burton Securities Inc. ("Bloom Burton") and includes Richardson Wealth Ltd. (together the "Agents"). In connection with the Financing and in accordance with the policies of the Exchange, the Agents will receive: (i) a cash fee equal to 6.0% of the gross proceeds raised in connection with the Financing; and (ii) warrants equal to 6.0% of the number of Subscription Receipts issued in connection with the Financing (the "Broker Warrants"). Each Broker Warrant shall entitle the holder thereof to buy one common share of the Resulting Issuer at the issue price in connection with the Arrangement. The term of the Broker Warrants shall be 24 months from the expected closing date of Financing. 51254637.6

Completion of the Arrangement is subject to, among other things, the approval of the Exchange, the Supreme Court of British Columbia and the shareholders of iCo and Satellos (collectively, the "Shareholders"). iCo shares will remain halted for trading pending the approval of the Arrangement by the Supreme Court of British Columbia, the Shareholders and the permission of the Exchange. Upon closing of the Arrangement, Satellos will become a wholly owned subsidiary of iCo, and the parties expect to complete an amalgamation of iCo and Satellos, with the resulting entity named "Satellos Bioscience Inc" (the "Resulting Issuer"). Upon the conclusion of the Financing, the holders of the Subscription Receipts will represent approximately 14% of the issued and outstanding common shares of the Resulting Issuer.

William Jarosz, the CEO of iCo noted, "We are very pleased by the success and expansion of the private placement. Following the private placement and Arrangement, the Company will be better capitalized around a more diverse set of clinical programs in various stages of development with very bright prospects for the future under the leadership of Satellos, a company addressing unmet needs in muscle wasting diseases, including Duchenne Muscular Dystrophy. We are also grateful for the support of existing investors participating in this financing who recognized the value of this new strategic direction for the Company."

Frank Gleeson, the CEO of Satellos, added: "We view the Financing as an extremely encouraging endorsement of the proposed business combination of iCo and Satellos and the potential for its new technology platform which aims to attack and treat a devastating series of muscle wasting diseases. Together with iCo management, we are focused on completing the Arrangement so that we can begin to execute on what we believe is an exciting plan for the future."

On April 23, 2021 InDex Pharmaceuticals Holding AB (publ) reported the Annual Report for 2020 (Press release, InDex Pharmaceuticals, APR 23, 2021, View Source [SID1234578390]). The Annual Report is attached as a PDF and is available on the company’s website, View Source

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The printed Annual Report is mailed to shareholders and other stakeholders who specifically request it. Send request to [email protected], or by mail to InDex Pharmaceuticals Holding AB (publ), Berzelius väg 13, 171 65 Solna, Sweden.

On April 23, 2021 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported U.S. Food and Drug Administration (FDA) approval of the VENTANA MMR RxDx Panel for advanced or recurrent endometrial cancer patients (Press release, Hoffmann-La Roche, APR 23, 2021, View Source [SID1234578389]). MMR is a molecular mechanism that functions to correct certain errors that can spontaneously occur during DNA replication. Testing can identify patients eligible for treatment with JEMPERLI (dostarlimab-gxly) monotherapy, an anti-PD1 immunotherapy from GlaxoSmithKline (GSK) that was approved by the FDA on 22 April 2021.

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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

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Endometrial cancer is the most common gynecologic cancer in the U.S. and the fourth most common cancer in women in North America.2 In addition, about 90,000 women globally die from endometrial cancer each year.1 There are limited treatment options for women whose disease progresses on or after first-line therapy and this is the first companion diagnostic to identify endometrial cancer patients eligible for anti-PD1 immunotherapy.

"We are excited to launch this companion diagnostic test with GSK to help recurrent or advanced endometrial cancer patients with limited treatment options," said Thomas Schinecker, CEO of Roche Diagnostics. "This test provides clinicians with an effective tool to identify patients best suited for treatment with GSK’s JEMPERLI, providing a new therapeutic option for women with MMR-deficient endometrial cancer whose disease progresses on or following initial chemotherapy treatment."

MMR deficiency is most common in endometrial cancer. This companion diagnostic (CDx) provides clinicians with a standardised testing option that uses a comprehensive panel of DNA mismatch repair (MMR) biomarkers tested by immunohistochemistry (IHC). FDA approval of the VENTANA MMR RxDx Panel provides clinicians with access to a fully automated, easy-to-use MMR test to identify patients who are eligible for therapy with JEMPERLI.

About the VENTANA MMR RxDx Panel
The VENTANA MMR RxDx Panel is a label expansion of Roche’s current on-market VENTANA MMR IHC Panel. VENTANA MMR RxDx Panel is a qualitative immunohistochemistry test intended for use in the assessment of mismatch repair (MMR) proteins (MLH1, PMS2, MSH2 and MSH6) in formalin-fixed, paraffin-embedded (FFPE) endometrial carcinoma tissue by light microscopy. The OptiView DAB IHC Detection Kit is used for MLH1, MSH2 and MSH6, and the OptiView DAB IHC Detection Kit with the OptiView Amplification Kit is used for PMS2 on a VENTANA BenchMark ULTRA instrument. DNA mismatch repair (MMR) proteins have been clinically proven to be predictive biomarkers for PD-1 targeted therapy; specifically, a loss of expression of one or more MMR proteins might predict an increased likelihood of response to such therapy.3,4,5 PD-1 inhibitors can be effective in cancers with a high frequency of MMR deficiency and/or microsatellite-instability, high (MSI-H) including endometrial cancer.3,5 MMR is a conserved molecular mechanism that functions to correct the improper base substitutions that spontaneously occur during DNA replication. Defects in the MMR machinery have been attributed to mutations in the MMR proteins.