On May 22, 2020 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and Sarah Cannon Research Institute (Sarah Cannon) reported that the first patient has been dosed in a first-in-human phase 1 study evaluating DS-6157, an investigational GPR20 directed antibody drug conjugate (ADC), in patients with advanced gastrointestinal stromal tumor (GIST) who have progressed on, or are intolerant to, standard treatment (Press release, Daiichi Sankyo, MAY 22, 2020, View Source [SID1234558406]).

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Treatment guidelines for patients with advanced GIST recommend surgery where possible and targeted therapy with tyrosine kinase inhibitors (TKIs).[i] For the majority of patients who eventually develop resistance to available therapies, there are few remaining options and new types of treatments may help address refractory disease.[ii]

"We are proud to build upon our relationship with Sarah Cannon to initiate this trial evaluating the potential of DS-6157 as a new type of targeted therapy for patients with advanced GIST," said Arnaud Lesegretain, Vice President Oncology R&D and Head, Alpha Portfolio, Daiichi Sankyo. "Based on preclinical assessments, biomarker research and the demonstrated portability of our DXd ADC technology, we believe that DS-6157 could potentially play a major role in the treatment of patients with GIST that is resistant to TKIs."

DS-6157 is the fifth DXd ADC from the oncology pipeline of Daiichi Sankyo to enter clinical development and the second being evaluated in the strategic oncology collaboration between Daiichi Sankyo and Sarah Cannon. DS-6157 was designed utilizing Daiichi Sankyo’s proprietary and portable DXd ADC technology to target and deliver chemotherapy inside cancer cells that express GPR20, particularly gastrointestinal stromal tumors, which highly express this target.[iii]

"Through the development of the DS-6157 targeted therapy, we are taking a critical step in finding more effective therapies for GIST patients," said Johanna Bendell, MD, Chief Development Officer and Director of Drug Development, Sarah Cannon Research Institute. "In partnership with Daiichi Sankyo, we look forward to providing access to this novel therapy for patients who vitally need these treatment options."

GIST is a rare soft tissue sarcoma that originates in the digestive tract, usually in the stomach. The annual worldwide incidence of GIST is estimated to be 10 to 15 cases per million, depending on the published series, and similar rates have been reported for Asian, European and Western countries.[iv]

GPR20 (G protein-coupled receptor 20) is a seven-pass transmembrane protein, which is selectively and abundantly expressed in GIST.3 GPR20 expression is detected in more than 80% of all GIST tumor samples irrespective of the number of prior lines of TKI treatments received.[v] In preclinical studies, DS-6157 demonstrated activity in GPR20 expressing tumor cells. No GPR20 directed therapies are currently approved for treatment of GIST or any cancer.

About the Study

The two-part, multicenter, open-label, first-in-human phase 1 study will investigate the safety, tolerability and efficacy of DS-6157 in adult patients with advanced/unresectable or metastatic GIST who have progressed on, or are intolerant to, standard treatment.

The first part of the study (dose escalation) will assess the safety and tolerability of increasing doses of DS-6157 to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE). This part of the trial will enroll approximately 40 patients with advanced/unresectable or metastatic GIST who have progressed on or are intolerant to imatinib and other TKI treatments. Enrollment into Part 1 will not be restricted to patients with evidence of GPR20 expression. The second part of the study (dose expansion) will evaluate the safety, tolerability and efficacy of DS-6157 at the established RDE. This part of the trial will include two cohorts. Cohort 1 will include approximately 30 patients with GIST who have progressed on imatinib and at least one post-imatinib treatment. Cohort 2 will include approximately 30 patients with GIST who progressed on imatinib but have not received additional systemic therapies.

The study will evaluate safety endpoints that include adverse events and efficacy endpoints including objective response rate, duration of response, disease control rate, clinical benefit rate, time to response, progression-free survival, and best percent change in target lesion by RECIST Version 1.1. Pharmacokinetic endpoints and exploratory biomarker endpoints will also be assessed.

A total of approximately 100 patients are expected to be enrolled in this study at approximately 10 sites in the U.S., Japan and other countries. For more information, please visit ClinicalTrials.gov.

About DS-6157

DS-6157 is a potential first-in-class GPR20 targeting ADC and the fifth DXd ADC in the oncology pipeline of Daiichi Sankyo to enter clinical development. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed utilizing Daiichi Sankyo’s proprietary DXd ADC technology, DS-6157 is comprised of a humanized anti-GPR20 monoclonal antibody, which is attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker.

Preclinical studies have shown that DS-6157 specifically binds to GPR20 on the surface of individual tumor cells. It is proposed that DS-6157 is then brought inside the cancer cell where lysosomal enzymes break down the tetrapeptide-based linker and release the DXd payload.

DS-6157 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our DXd antibody drug conjugate (ADC) technology, our powerful research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.

On May 22, 2020 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca’s ENHERTU (fam-trastuzumab deruxtecan-nxki) has been granted Orphan Drug Designation (ODD) in the U.S. for the treatment of patients with gastric cancer, including gastroesophageal junction cancer (Press release, Daiichi Sankyo, MAY 22, 2020, View Source [SID1234558405]).

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The U.S. Food and Drug Administration (FDA) grants ODD to medicines intended for the treatment, diagnosis or prevention of rare diseases of disorders that affect fewer than 200,000 people in the U.S.

An estimated 27,600 new cases of gastric cancer will be diagnosed this year, and the disease could lead to more than 11,000 deaths in the U.S. in 2020.[1]

The phase 2 DESTINY-Gastric01 trial demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of objective response rate (ORR) and the secondary endpoint of overall survival (OS) for patients with HER2 positive metastatic gastric or gastroesophageal cancer treated with ENHERTU, a HER2 directed antibody drug conjugate (ADC), versus physician’s choice of chemotherapy (irinotecan or paclitaxel monotherapy).

The overall safety and tolerability profile of ENHERTU in DESTINY-Gastric01 was consistent with that seen in the phase 1 gastric cancer trial in which the most common adverse events (≥30%, any grade) were hematologic and gastrointestinal including neutrophil count decrease, anemia, nausea and decreased appetite. There were cases of drug-related interstitial lung disease (ILD) and pneumonitis, the majority of which were grade 1 and 2 with two grade 3 and one grade 4. No ILD-related deaths (grade 5) occurred in patients with gastric cancer in the phase 1 trial or in the DESTINY-Gastric01 trial.

The research results of DESTINY-Gastric01 will be presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) (ASCO20) Virtual Scientific Program.

Earlier this month, ENHERTU received two Breakthrough Therapy Designations from the FDA for the treatment of patients with HER2 positive unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma who have received two or more prior regimens including trastuzumab, and for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.

ENHERTU also received SAKIGAKE designation in March 2018 from Japan’s Ministry of Health, Labour and Welfare (MHLW) for potential use in HER2 positive gastric cancer, and a supplemental New Drug Application was recently submitted to the Japan MHLW.

About HER2

HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers. In some tumors, HER2 overexpression is associated with a specific HER2 gene alteration known as HER2 amplification and is often associated aggressive disease and poorer prognosis.[2]

About Gastric Cancer

Gastric (stomach) cancer is the fifth most common cancer worldwide and the third leading cause of cancer mortality; there were approximately one million new cases reported in 2018 and 783,000 deaths.[3] In the U.S., it is estimated that 27,600 new cases of stomach cancer will be diagnosed in 2020 and more than 11,000 people will die from the disease.1

Approximately one in five gastric cancers are HER2 positive.[4] Gastric cancer is usually diagnosed in the advanced stage in the U.S., but even when diagnosed in earlier stages of the disease the survival rate remains modest.[5] Recommended first-line treatment for HER2 positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve outcomes when added to chemotherapy.[6] For gastric cancer that progresses on first-line treatment, trastuzumab has not shown any further benefit and there are no other approved HER2 targeted medicines.6

DESTINY-Gastric01

DESTINY-Gastric01 is a phase 2, open-label, multi-center trial assessing the safety and efficacy of ENHERTU in a primary cohort of 188 patients from Japan and South Korea with HER2 expressing advanced gastric or gastroesophageal junction adenocarcinoma (defined as IHC3+ or IHC2+/ISH+) who have progressed on two or more prior treatment regimens including fluoropyrimidine (5-FU), platinum chemotherapy and trastuzumab. Patients were randomized 2:1 to receive ENHERTU or investigator’s choice of chemotherapy (paclitaxel or irinotecan monotherapy). Patients were treated with ENHERTU 6.4 mg/kg once every three weeks or chemotherapy. The primary endpoint of the study is ORR as assessed by an independent review committee. Secondary endpoints include OS, progression-free survival, duration of response, disease control rate and time to treatment failure as well as pharmacokinetic and safety endpoints.

About ENHERTU

ENHERTU (fam-trastuzumab deruxtecan-nxki in the U.S. only; trastuzumab deruxtecan outside the U.S.) is a HER2 directed ADC and is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced program in AstraZeneca’s ADC Scientific platform.

ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Designed using Daiichi Sankyo’s proprietary DXd ADC technology, ENHERTU is comprised of a HER2 monoclonal antibody attached to a novel topoisomerase I inhibitor payload by a tetrapeptide-based linker.

ENHERTU (5.4 mg/kg) is approved in the U.S. and Japan for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who received two or more prior anti-HER2 based regimens based on the DESTINY-Breast01 trial.

ENHERTU has been approved for use only in the U.S. and Japan. ENHERTU has not been approved in the EU, or countries outside of Japan and the United States, for any indication. It is an investigational agent globally for various indications. Safety and effectiveness have not been established for the subject proposed use.

About the ENHERTU Clinical Development Program

A comprehensive development program for ENHERTU is underway globally with six pivotal trials evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2 targetable cancers including breast, gastric and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.

About the Collaboration between Daiichi Sankyo and AstraZeneca

In March 2019, Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU worldwide, except in Japan where Daiichi Sankyo maintains exclusive rights. Daiichi Sankyo is solely responsible for the manufacturing and supply.

U.S. FDA-Approved Indication for ENHERTU

ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting.

This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

WARNING: INTERSTITIAL LUNG DISEASE and EMBRYO-FETAL TOXICITY

●　Interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported with ENHERTU. Monitor for and promptly investigate signs and symptoms including cough, dyspnea, fever, and other new or worsening respiratory symptoms. Permanently discontinue ENHERTU in all patients with Grade 2 or higher ILD/pneumonitis. Advise patients of the risk and to immediately report symptoms.

●　Exposure to ENHERTU during pregnancy can cause embryo-fetal harm. Advise patients of these risks and the need for effective contraception.

Contraindications
None.

WARNINGS AND PRECAUTIONS

Interstitial Lung Disease / Pneumonitis
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ENHERTU. In clinical studies, of the 234 patients with unresectable or metastatic HER2-positive breast cancer treated with ENHERTU, ILD occurred in 9% of patients. Fatal outcomes due to ILD and/or pneumonitis occurred in 2.6% of patients treated with ENHERTU. Median time to first onset was 4.1 months (range: 1.2 to 8.3).

Advise patients to immediately report cough, dyspnea, fever, and/or any new or worsening respiratory symptoms. Monitor patients for signs and symptoms of ILD. Promptly investigate evidence of ILD. Evaluate patients with suspected ILD by radiographic imaging. Consider consultation with a pulmonologist. For asymptomatic ILD/pneumonitis (Grade 1), interrupt ENHERTU until resolved to Grade 0, then if resolved in ≤28 days from date of onset, maintain dose. If resolved in >28 days from date of onset, reduce dose one level. Consider corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥0.5 mg/kg prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), permanently discontinue ENHERTU. Promptly initiate corticosteroid treatment as soon as ILD/pneumonitis is suspected (e.g., ≥1 mg/kg prednisolone or equivalent). Upon improvement, follow by gradual taper (e.g., 4 weeks).

Neutropenia

Severe neutropenia, including febrile neutropenia, can occur in patients treated with ENHERTU. Of the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, a decrease in neutrophil count was reported in 30% of patients and 16% had Grade 3 or 4 events. Median time to first onset was 1.4 months (range: 0.3 to 18.2). Febrile neutropenia was reported in 1.7% of patients.

Monitor complete blood counts prior to initiation of ENHERTU and prior to each dose, and as clinically indicated. Based on the severity of neutropenia, ENHERTU may require dose interruption or reduction. For Grade 3 neutropenia (Absolute Neutrophil Count [ANC] <1.0 to 0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less, then maintain dose. For Grade 4 neutropenia (ANC <0.5 x 109/L) interrupt ENHERTU until resolved to Grade 2 or less. Reduce dose by one level. For febrile neutropenia (ANC <1.0 x 109/L and temperature >38.3ºC or a sustained temperature of ≥38ºC for more than 1 hour), interrupt ENHERTU until resolved. Reduce dose by one level.

Left Ventricular Dysfunction

Patients treated with ENHERTU may be at increased risk of developing left ventricular dysfunction. Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including ENHERTU. In the 234 patients with unresectable or metastatic HER2-positive breast cancer who received ENHERTU, two cases (0.9%) of asymptomatic LVEF decrease were reported. Treatment with ENHERTU has not been studied in patients with a history of clinically significant cardiac disease or LVEF <50% prior to initiation of treatment.

Assess LVEF prior to initiation of ENHERTU and at regular intervals during treatment as clinically indicated. Manage LVEF decrease through treatment interruption. Permanently discontinue ENHERTU if LVEF of <40% or absolute decrease from baseline of >20% is confirmed. When LVEF is >45% and absolute decrease from baseline is 10-20%, continue treatment with ENHERTU. When LVEF is 40-45% and absolute decrease from baseline is <10%, continue treatment with ENHERTU and repeat LVEF assessment within 3 weeks. When LVEF is 40-45% and absolute decrease from baseline is 10-20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF has not recovered to within 10% from baseline, permanently discontinue ENHERTU. If LVEF recovers to within 10% from baseline, resume treatment with ENHERTU at the same dose. When LVEF is <40% or absolute decrease from baseline is >20%, interrupt ENHERTU and repeat LVEF assessment within 3 weeks. If LVEF of <40% or absolute decrease from baseline of >20% is confirmed, permanently discontinue ENHERTU. Permanently discontinue ENHERTU in patients with symptomatic congestive heart failure.

Embryo-Fetal Toxicity
ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of ENHERTU. Advise females of reproductive potential to use effective contraception during treatment and for at least 7 months following the last dose of ENHERTU. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months after the last dose of ENHERTU.

Adverse Reactions
The safety of ENHERTU was evaluated in a pooled analysis of 234 patients with unresectable or metastatic HER2-positive breast cancer who received at least one dose of ENHERTU 5.4 mg/kg in DESTINY-Breast01 and Study DS8201-A-J101. ENHERTU was administered by intravenous infusion once every three weeks. The median duration of treatment was 7 months (range: 0.7 to 31).

Serious adverse reactions occurred in 20% of patients receiving ENHERTU. Serious adverse reactions in >1% of patients who received ENHERTU were interstitial lung disease, pneumonia, vomiting, nausea, cellulitis, hypokalemia, and intestinal obstruction. Fatalities due to adverse reactions occurred in 4.3% of patients including interstitial lung disease (2.6%), and the following events occurred in one patient each (0.4%): acute hepatic failure/acute kidney injury, general physical health deterioration, pneumonia, and hemorrhagic shock.

ENHERTU was permanently discontinued in 9% of patients, of which ILD accounted for 6%. Dose interruptions due to adverse reactions occurred in 33% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose interruption were neutropenia, anemia, thrombocytopenia, leukopenia, upper respiratory tract infection, fatigue, nausea, and ILD. Dose reductions occurred in 18% of patients treated with ENHERTU. The most frequent adverse reactions (>2%) associated with dose reduction were fatigue, nausea, and neutropenia.

The most common adverse reactions (frequency ≥20%) were nausea (79%), fatigue (59%), vomiting (47%), alopecia (46%), constipation (35%), decreased appetite (32%), anemia (31%), neutropenia (29%), diarrhea (29%), leukopenia (22%), cough (20%), and thrombocytopenia (20%).

Use in Specific Populations

Pregnancy: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise patients of the potential risks to a fetus. There are clinical considerations if ENHERTU is used in pregnant women, or if a patient becomes pregnant within 7 months following the last dose of ENHERTU.

Lactation: There are no data regarding the presence of ENHERTU in human milk, the effects on the breastfed child, or the effects on milk production. Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with ENHERTU and for 7 months after the last dose.

Females and Males of Reproductive Potential: Pregnancy testing: Verify pregnancy status of females of reproductive potential prior to initiation of ENHERTU. Contraception: Females: ENHERTU can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 7 months following the last dose. Males: Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ENHERTU and for at least 4 months following the last dose. Infertility: ENHERTU may impair male reproductive function and fertility.

Pediatric Use: Safety and effectiveness of ENHERTU have not been established in pediatric patients.

Geriatric Use: Of the 234 patients with HER2-positive breast cancer treated with ENHERTU 5.4 mg/kg, 26% were ≥65 years and 5% were ≥75 years. No overall differences in efficacy were observed between patients ≥65 years of age compared to younger patients. There was a higher incidence of Grade 3-4 adverse reactions observed in patients aged ≥65 years (53%) as compared to younger patients (42%).

Hepatic Impairment: In patients with moderate hepatic impairment, due to potentially increased exposure, closely monitor for increased toxicities related to the topoisomerase inhibitor.

On May 21, 2020 Midatech Pharma PLC (AIM: MTPH.L; Nasdaq: MTP), an R&D biotechnology company focused on delivering innovative oncology and rare disease products to patients, reported the closing of its previously announced registered direct offering (the "Offering") of 1,818,182 of its American Depositary Shares ("ADSs") (each ADS representing five of the Company’s ordinary shares (the "New Ordinary Shares")) at a purchase price of US$1.65 per ADS (equivalent to £0.27 per New Ordinary Share). Additionally, in a concurrent private placement, the Company issued to the investors unregistered warrants to purchase up to 1,818,182 ADSs ("Warrant ADSs") (Press release, Midatech Pharma, MAY 21, 2020, View Source [SID1234562694]). The net proceeds to Midatech from the offering are expected to be approximately US$2.6 million (£2.1 million), after deducting the placement agent’s fees and other estimated offering expenses. Midatech intends to use the proceeds from the offering to fund the clinical development program of MTX110, its product for DIPG and potentially other pediatric brain cancers, develop an internal pipeline of Q-Sphera formulation for partnering, for working capital and for general corporate purposes.

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H.C Wainwright & Co. acted as the exclusive placement agent for the offering.

The warrants have an exercise price of US$2.05 per ADS (equivalent to £0.34 per New Ordinary Share), subject to adjustment as set forth therein, and will be immediately exercisable. The warrants will expire five years and one-half years from the issuance date.

The ADSs described above (but not the warrants or the Warrant ADSs) were offered pursuant to a shelf registration statement (File No. 333-233901) which became effective on October 21, 2019. The offering of the ADSs was made by means of a prospectus, including a prospectus supplement, forming part of the effective registration statement. Copies of the prospectus supplement and the accompanying prospectus relating to the offering may be obtained from the SEC’s website at View Source or from H.C. Wainwright & Co., LLC, 430 Park Avenue, 3rd Floor, New York, NY 10022, by calling (646) 975-6996 or by emailing [email protected].

The warrants described above were offered in a private placement under Section 4(a)(2) of the Securities Act of 1933, as amended (the "Act"), and Regulation D promulgated thereunder and, along with the Warrant ADSs issuable upon their exercise, have not been registered under the Act, and may not be offered or sold in the United States absent registration with the SEC or an applicable exemption from such registration requirements and applicable state securities laws.

The Company expects its previously announced placing ("Placing") to certain investors in the United Kingdom of 6,666,666 units ("Units"), with each Unit comprising one ordinary share and one warrant exercisable for one ordinary share, at an issue price of £0.27 per Unit, to close on or about 22 May 2020.

Application has been made for admission of the 15,757,576 new ordinary shares issued in the Offering, and to be issued in the Placing, for trading on AIM, which is anticipated to occur at 8:00am on 22 May 2020 ("Admission"). The new ordinary shares will rank pari passu with the existing ordinary shares of the Company.

Following closing of the Offering, the Company’s issued ordinary share capital will consist of 32,585,891 ordinary shares. The Company does not hold any shares in treasury. Therefore, the total number of ordinary shares with voting rights in Midatech is 32,585,891.

The above figure of 32,585,891 may be used by shareholders as the denominator for the calculations by which they will determine if they are required to notify their interest in, or a change to their interest in the Company under the FCA’s Disclosure Guidance and Transparency Rules.

On May 21, 2020, Geron Corporation (the "Company") reported that it entered into an underwriting agreement (the "Underwriting Agreement") with Stifel, Nicolaus & Company, Incorporated and MTS Securities, LLC, as representatives of the several underwriters named therein (collectively, the "Underwriters"), relating to the issuance and sale (the "Offering") of 107,049,375 shares of the Company’s common stock ("Common Stock"), and pre-funded warrants to purchase 8,335,239 shares of Common Stock (the "Pre-Funded Warrants"), together with accompanying warrants to purchase 57,692,307 shares of Common Stock (the "Common Stock Warrants", and together with the Pre-Funded Warrants, the "Warrants") (Filing, 8-K, Geron, MAY 21, 2020, View Source [SID1234558472]). The combined offering price to the public of each share of Common Stock and accompanying Common Stock Warrant is $1.30. The combined offering price to the public of each Pre-Funded Warrant and accompanying Common Stock Warrant is $1.299. The gross proceeds to the Company from the Offering are expected to be approximately $150 million, before deducting underwriting discounts and estimated offering expenses. All of the securities in the Offering are being sold by the Company. The Offering is expected to close on May 27, 2020, subject to satisfaction of customary closing conditions.

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Each Pre-Funded Warrant will have an initial exercise price per share of $0.001, subject to certain adjustments. The Pre-Funded Warrants will be exercisable immediately and may be exercised at any time until all of the Pre-Funded Warrants are exercised in full. A holder (together with its affiliates and other attribution parties) may not exercise any portion of a Pre-Funded Warrant to the extent that immediately prior to or after giving effect to such exercise the holder would own more than 9.99% of the Company’s outstanding Common Stock immediately after exercise, which percentage may be changed at the holder’s election to a lower or higher percentage not in excess of 19.99% (if exceeding such percentage would result in a change of control under Nasdaq Listing Rule 5635(b) or any successor rule) upon 61 days’ notice to the Company subject to the terms of the Pre-Funded Warrants.

Each Common Stock Warrant will have an initial exercise price per share of $1.30, subject to certain adjustments. The Common Stock Warrants will be exercisable immediately and will expire on the earlier to occur of (a) the date that is 30 business days following the date on which the Company first issues a press release disclosing, if applicable, positive top-line safety and efficacy results from the Phase 3 portion of IMerge, the Company’s Phase 2/3 clinical trial of imetelstat for the treatment of patients with Low or Intermediate-1 risk myelodysplastic syndromes (or, if such date is not a business day, then the next business day following such date) and (b) December 31, 2025. A holder (together with its affiliates and other attribution parties) may not exercise any portion of a Common Stock Warrant to the extent that immediately prior to or after giving effect to such exercise the holder would own more than 9.99% of the Company’s outstanding Common Stock immediately after exercise, which percentage may be changed at the holder’s election to a lower or higher percentage not in excess of 19.99% (if exceeding such percentage would result in a change of control under Nasdaq Listing Rule 5635(b) or any successor rule) upon 61 days’ notice to the Company subject to the terms of the Common Stock Warrants.

The Offering is being made pursuant to the Company’s shelf registration statement on Form S-3 filed with the Securities and Exchange Commission (the "SEC") on May 24, 2018, which became effective on July 12, 2018 (Registration Statement No. 333-225184), and a prospectus supplement thereunder (the "Prospectus Supplement"), and pursuant to a related registration statement on Form S-3 (No. 333-238595) filed with the SEC pursuant to Rule 462(b) of the Securities Act of 1933, as amended (the "Securities Act").

The Underwriting Agreement contains customary representations, warranties and agreements by the Company, customary conditions to closing, indemnification obligations of the Company and the Underwriters, including for liabilities arising under the Securities Act other obligations of the parties and termination provisions. The representations, warranties and covenants contained in the Underwriting Agreement were made only for the purposes of such agreement and as of specific dates, and were solely for the benefit of the parties to such agreement.

The foregoing descriptions of the terms of the Underwriting Agreement, Pre-Funded Warrants and Common Stock Warrants are each qualified in their entirety by reference to the Underwriting Agreement, form of Pre-Funded Warrant and form of Common Stock Warrant, respectively, which are attached as Exhibit 1.1, Exhibit 4.1 and Exhibit 4.2 hereto, respectively, and incorporated by reference herein.

On May 21, 2020 SutroVax, Inc., a next-generation vaccine company, reported that it has changed its name to Vaxcyte, Inc (Press release, Sutro Biopharma, MAY 21, 2020, View Source [SID1234558459]). The new name more accurately reflects the Company’s mission to improve global health by developing superior and novel vaccines designed to prevent or treat some of the most common and deadly infectious diseases worldwide.

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"We are committed to developing superior vaccines that provide broader protection than what is available currently and to developing novel vaccines that target pathogens for which no approved vaccines exist," said Grant Pickering, Chief Executive Officer and Co-founder of Vaxcyte. "As we move our business forward and prepare for our lead pneumococcal conjugate vaccine candidate, VAX-24, to advance into clinical trials, we believe now is the time to make a change to a new name that reflects our path ahead and our unique expertise."

The new Vaxcyte name and logo connote the Company’s focus on developing vaccines to prevent or treat some of the most common and deadly infectious diseases worldwide, utilizing its exclusively-licensed cell-free protein synthesis platform and its proprietary know-how. As an example, Vaxcyte has leveraged this platform and know-how, utilizing site-specific conjugation, to develop its lead pneumococcal conjugate vaccine program to incite T-cell and B-cell-mediated (leukocyte) immune responses.

VAX-24, formerly referred to as SVX-24 and the lead vaccine candidate in Vaxcyte’s pipeline, is a preclinical, 24-valent pneumococcal conjugate vaccine (PCV) that includes 11 incremental strains over and above the 13 strains in Prevnar 13 and covers the 23 stains contained in Pneumovax 23, which together make up today’s standard of care vaccination regimen for adults. Vaxcyte expects to submit an Investigational New Drug application for VAX-24 to the U.S. Food and Drug Administration in the second half of 2021 to evaluate it for the prevention of invasive pneumococcal disease (IPD).

Vaxcyte’s pipeline also includes VAX-XP, a PCV with an expanded breadth of coverage of at least 30 strains, including newly emerging strains responsible for IPD and antibiotic resistance, as well as a novel conjugate vaccine designed to prevent Group A Strep infections and a novel protein-based therapeutic vaccine designed to slow or stop the progression of periodontal disease by targeting the keystone pathogen responsible for this chronic, oral inflammatory disease.