On April 12, 2021 EMD Serono, the Healthcare business sector of Merck KGaA, Darmstadt, Germany in the US and Canada, reported key clinical advancements for berzosertib (M6620), an investigational, potent and selective ataxia telangiectasia and Rad3-related (ATR) inhibitor (Press release, EMD Serono, APR 12, 2021, View Source [SID1234577932]). Berzosertib is the leading asset in the company’s DNA damage response (DDR) inhibitor program and one of the most advanced ATR inhibitors in oncology clinical development industry-wide.

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Results from a Phase II proof-of-concept study conducted by the US National Cancer Institute (NCI) (NCT02487095)* and published in Cancer Cell showed that berzosertib in combination with the chemotherapy topotecan resulted in an objective response rate (ORR) of 36% among patients with relapsed small cell lung cancer (SCLC), including durable responses among a majority of responding patients with platinum-resistant disease.1 The NCI is also conducting a separate Phase II trial of berzosertib in combination with topotecan versus topotecan monotherapy in SCLC that has relapsed (NCT03896503)* which is currently the only randomized controlled trial of the combination in this population.

EMD Serono also initiated a global Phase II study to further assess berzosertib in combination with topotecan for the treatment of relapsed, platinum-resistant SCLC (DDRiver SCLC 250). The first patient has been enrolled in the open-label, single-arm trial, which plans to include approximately 80 participants at about 41 study sites across Asia, Europe, and North America.

"Small-cell neuroendocrine cancers, including small cell lung cancer, are associated with very poor prognoses, and are a major clinical challenge with no effective therapeutic options. In this study, the combination of berzosertib and topotecan showed higher than expected response rates and durable responses in patients with platinum-resistant SCLC, highlighting the therapeutic potential of this combination for patients with this recalcitrant cancer type," said Anish Thomas, MBBS, M.D., investigator and NIH Lasker Clinical Research Scholar at the Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, and lead investigator of the study. Dr. Thomas is collaborating with Merck KGaA, Darmstadt, Germany through a Cooperative Research and Development Agreement (CRADA).

Topotecan is the chemotherapeutic standard-of-care for second-line treatment of SCLC and is associated with low response rates, particularly in platinum-resistant disease.1 Findings from the NCI study highlight the vulnerability of SCLC tumors to ATR inhibition as a result of high levels of replication stress and the potential for the combination of berzosertib and topotecan to enhance the efficacy of topotecan among chemotherapy-resistant patients.1 These data build on earlier published results from Phase I of this study which also suggested a potential benefit of this combination in participants with platinum-resistant SCLC.2

"We are encouraged by these promising results, and are eager to further investigate berzosertib in a potentially registrational trial in SCLC as part of our front-running leadership in the research of DNA damage response," said Danny Bar-Zohar, M.D., Global Head of Development for the Healthcare business sector of Merck KGaA, Darmstadt, Germany.

These results are in addition to results from an NCI-sponsored open-label, randomized, Phase II study (NCI protocol 9944) evaluating berzosertib in combination with gemcitabine versus gemcitabine alone for the treatment of recurrent, platinum-resistant high-grade serous ovarian cancer, which were published in The Lancet Oncology in 2020. The study, conducted through a separate CRADA between NCI and Merck KGaA, Darmstadt, Germany, showed a benefit of adding berzosertib to gemcitabine in this treatment setting including improvement in progression-free survival, and is the first randomized study of an ATR inhibitor in any tumor type.3

As part of its new DDRiver Clinical Trials program, the company is investigating DDR inhibitor targeting pathways across more than ten trials in various tumor types.

NCI Study Results
In the Phase II single-arm study of berzosertib plus topotecan in patients with SCLC whose disease had progressed on prior therapy, 25 patients were evaluable for the primary endpoint of ORR as measured by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1), and the secondary endpoints of progression-free survival (PFS) and overall survival (OS) and duration of response (DOR). Berzosertib 210 mg/m2 was administered intravenously on days 2 and 5, and topotecan 1.25 mg/m2 was given intravenously on days 1 through 5 in 21-day cycles; treatment continued until disease progression.1

The confirmed ORR was 36% (95% CI, 18.0–57.5; all partial response).1 Most patients (68.0%) experienced tumor regressions.1 Responses were observed in patients with both platinum-sensitive (60.0% [95% CI, 14.7–94.7]) and platinum-resistant (30.0% [95% CI, 11.9–54.3]) disease.1 Median DOR was 6.4 months (95% CI, 1.1–14.3), and four of the six (66.7%) responders with platinum-resistant SCLC had DOR of more than 6 months.1 Median PFS was 4.8 months (95% CI, 2.8–7.4), with PFS rates at 4 months and 6 months of 60.0% (95% CI, 38.4-76.1) and 36.0% (95% CI, 18.2–54.2).1 Median OS was 8.5 months (95% CI, 5.6-13.6);1 OS rates at 6 months and 12 months were 68.0% (95% CI, 46.1–82.5) and 32.0% (95% CI, 15.2–50.2).1

Among 26 patients evaluable for safety, the most common treatment-related adverse events (AE) were anemia (96.2%), lymphopenia (96.2%), thrombocytopenia (92.3%), and neutropenia (50.0%), nausea (50.0%) and vomiting (42.3%).1 The most common grade 3 or 4 AEs were lymphopenia (69.2%), thrombocytopenia (57.7%), anemia (53.8%), and neutropenia (15.4%).1 No treatment-related deaths occurred.1 Most AEs were attributable to topotecan, which as monotherapy is associated with a high frequency of myelosuppression.1,4

*Additional information on these clinical trials are available at clinicaltrials.gov, through identifier numbers NCT02487095 and NCT03896503. Patients interested in enrolling in these berzosertib and topotecan combination clinical trials can call the National Cancer Institute’s toll-free number 1-800-4-Cancer (1-800-422-6237) (TTY: 1-800-332-8615).

About Small Cell Lung Cancer
Of the estimated 1.6 million new lung cancer cases diagnosed worldwide each year, approximately 15% are SCLC.5 SCLC is the most aggressive form of lung cancer, characterized by a rapid doubling time and widespread metastases,6 and approximately two-thirds of patients present with extensive disease that has metastasized, when first found.7 The median survival time for patients with SCLC is 7 months,5 and the relative five-year survival rate is just 7%.8

About Berzosertib
Berzosertib is an investigational, potent and selective inhibitor of the ataxia telangiectasia and Rad3-related (ATR) protein that blocks ATR activity in cells. Berzosertib is the first ATR inhibitor evaluated in a randomized clinical trial in any tumor type,3 and it is the lead candidate in EMD Serono’s DNA Damage Response (DDR) inhibitor portfolio. It is currently being investigated in a number of internal and external studies with early phase I/II data in small cell lung cancer, ovarian cancer, and various solid tumors.3,9 Berzosertib, formerly known as VX-970, was licensed from Vertex Pharmaceuticals in 2017. Berzosertib is not approved for any use anywhere in the world.

References

Thomas A, Takahashi N, Rajapakse V, et al. Therapeutic targeting of ATR yields durable regressions in small cell lung cancers with high replication stress. Cancer Cell 39 (4), 2021, pp.566-579.
Thomas, A., Redon, C. E., Sciuto, L., Padiernos, E., Ji, J., Lee, M. J., Yuno, A., Lee, S., Zhang, Y., Tran, L., et al. (2018). Phase I Study of ATR Inhibitor M6620 in Combination With Topotecan in Patients With Advanced Solid Tumors. J Clin Oncol36, 1594-1602.
Konstantinopoulos PA, et al. Berzosertib plus gemcitabine versus gemcitabine alone in platinum-resistant high-grade serous ovarian cancer: a multicentre, open-label, randomised, phase 2 trial. Lancet Oncol. 2020 Jul;21(7):957-968. doi: 10.1016/S1470-2045(20)30180-7. Epub 2020 Jun 15. PMID: 32553118.
von Pawel, J., Schiller, J. H., Shepherd, F. A., Fields, S. Z., Kleisbauer, J. P., Chrysson, N. G., Stewart, D. J., Clark, P. I., Palmer, M. C., Depierre, A., et al. (1999). Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol 17, 658-667.
Wang S, et al. Survival changes in patients with small cell lung cancer and disparities between different sexes, socioeconomic statuses and ages. Sci Rep. 2017;(1):1339.
Byers LA, Rudin CM. Small cell lung cancer: where do we go from here? Cancer. 2015;121(5):664-72.
American Cancer Society.Small Cell Lung Cancer Stages. View Source (Accessed April 8, 2021).
American Cancer Society. Lung Cancer Survival Rates. View Source (Accessed April 8, 2021).
Yap TA, et al. Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors. J Clin Oncol. 2020 Sep 20;38(27):3195-3204. doi: 10.1200/JCO.19.02404. Epub 2020 Jun 22. PMID: 32568634; PMCID: PMC7499606.
All Merck KGaA, Darmstadt, Germany, press releases are distributed by e-mail at the same time they become available on the EMD Group Website. In case you are a resident of the USA or Canada please go to www.emdgroup.com/subscribe to register again for your online subscription of this service as our newly introduced geo-targeting requires new links in the email. You may later change your selection or discontinue this service.

On April 12, 2021 Onxeo S.A. (Euronext Growth Paris: ALONX; Nasdaq First North Growth Copenhague: ONXEO, a clinical-stage biotechnology company specializing in the development of innovative drugs targeting tumor DNA Damage Response (DDR), in particular against rare or resistant cancers, reported the result of its capital increase through the issuance of new shares (the "New Shares") with shareholders’ preferential subscription rights (PSR), whose subscription took place from March 19 to March 31, 2021 included in France and from March 19 to March 26, 2021 included in Denmark (Press release, Onxeo, APR 12, 2021, View Source [SID1234580416]).

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The gross amount of the capital increase, including the issue premium, amounted to 9.7 million euros and resulted in the creation of 13,677,125 New Shares, at a subscription price per share of 0.71 euro (5.287 DKK on the basis of an exchange rate of 7.447 DKK for 1 euro on March 9, 2021).

The proceeds from this issue of New Shares are intended to finance primarily the expansion and acceleration of the clinical development of AsiDNA, in particular in combination with other anti-cancer agents.

The Company also intends to:

continue the optimization and preclinical development of new candidates selected on the platON platform,
optimize pharmaceutical development and compound manufacturing operations, and
more generally, finance the Company’s operations.
Judith Greciet, CEO of Onxeo, said: "We would like to thank all our investors, both historical and new, who have contributed to the success of this fundraising. The renewed confidence in our long-term strategy by our two core shareholders, Financière de la Montagne and Invus, as well as by many other shareholders, secures the ramp-up of our development and extends our visibility until the end of 2022. With the funds raised, the Company will accelerate the development of AsiDNA with other clinical trials, notably in non-small cell lung cancer, with a phase 2 study designed to be extended as a potential pivotal trial. The clinical program should also include the United States as part of the acceleration plan. Additionally, we will expand our portfolio with other compounds from our platON platform."

The Board of Directors of Onxeo, in its meeting on April 12, 2021, recorded the amount of subscriptions and decided on the final terms of the capital increase with preferential subscription rights of shareholders decided on March 9, 2021.

RESULT OF THE RIGHT ISSUE

At the end of the subscription period, subscriptions totaled 13,677,125 shares, divided as follows:

6,111,797 New Shares were subscribed on an irreducible basis;
7,565,328 Shares News were requested on a free basis.
As the Company has decided to exercise the extension clause provided for in the 20th resolution of the General Meeting of June 19, 2020 for 4.8% of the initial offer, the new shares applied for on a free basis were fully allocated.

Consequently, the gross amount of the capital increase, including issue premium, amounts to 9,710,758.75 euros and results in the issue of 13,677,125 new shares, at a unit subscription price of 0.71 euros, corresponding to a subscription rate of approximately 104.8%.

The Company’s share capital following the capital increase will amount to 22,998,733.75 euros, divided into 91,994,935 shares with a par value of 0.25 euros each.

The settlement-delivery of the New Shares and their admission to trading on Euronext Growth Paris and Nasdaq First North Growth Copenhagen are scheduled for April 16 and April 19, 2021, respectively.

The New Shares will carry dividend rights and will be traded on the same quotation line as the existing shares (ISIN FR0010095596).

Impact of the issue on the shareholding structure

The following table presents the distribution of capital, to the Company’s knowledge, before and after the completion of the capital increase.

The commitments of the existing shareholders, Financière de la Montagne and Invus Public Equities LP, were fully subscribed for a total amount of 7 million euros, respectively 3 and 4 of which approximately 2.1 million euros were on an irreducible basis and 4.9 million euros on a free basis. The subscriptions of other investors thus amount to about 2.7 million euros.

Actionnaires Number of shares before the issue % of capital and voting rights(1) shares before the issue Number of shares after the issue % of capital and voting rights(1) shares after the issue
Financière de la Montagne 10,462,560 13.36% 14,708,767 15.99%
Invus Public Equities LP 8,397,270 10.72% 14,031,073 15.25%
Free float 59,457,980 75.92% 63,255,095 68.76%
Total 78,317,810 100.00% 91,994,935 100.00%
Theoretical voting rights. All shares have the same voting rights, with the exception of treasury shares held by the Company.
DILUTION

For information purposes, the impact of the issue on the capital ownership of a shareholder holding 1% of the Company’s share capital prior to the issue and who did not subscribe to the issue (calculations based on a number of 78,317,810 shares making up the Company’s share capital at December 31, 2020) is as follows:

Shareholder’s interest (%)
(en euro par action) Non-diluted basis Diluted basis (1)
Before issue of New Shares 1.00 0.95
After issue of 13,677,125 New Shares 0.85 0.81
(1) Taking into account the 4,335,740 options and warrants giving access to the share capital granted and outstanding as of today.

INDICATIVE TIMETABLE OF THE OPERATION

April 16, 2021 Issuance of New Shares – Settlement and Delivery.
April 19, 2021 Admission of the New Shares to trading on Euronext Growth Paris and Nasdaq First North Growth Copenhagen.

Contributors

– Invest Securities acted as Lead Manager and Bookrunner of the transaction.

– Invest Corporate Finance acted as Listing Sponsor.

– Nordea Denmark, a subsidiary of Nordea Bank Abp, Finland, acted as underwriting agent in Denmark.

AVAILABILITY OF THE PROSPECTUS

The Prospectus, having received the approval n°21-063 dated March 9, 2021 from the Autorité des marchés financiers ("AMF"), consists of (i) the Universal Registration Document of Onxeo filed with the AMF on April 27, 2020 under number D.20-0362 (the "Universal Registration Document"), (ii) the Amendment to the Universal Registration Document, filed with the AMF on March 9, 2021 under number D.20-0362-A01, (iii) a Securities Note and (iv) a summary of the Prospectus (included in the Securities note).

Copies of the Prospectus are available free of charge at the registered office of Onxeo, 49, boulevard du Général Martial Valin – 75015 Paris. The Prospectus may also be consulted on the websites of the AMF (www.amf-france.org) and Onxeo (www.onxeo.com) and from the Lead Manager and Bookrunner.

In connection with the opening of the public offering in Denmark, an unofficial translation into English of all the documents constituting the prospectus has also been prepared by the Company. In the event of any discrepancy between the French prospectus and the English translation, the French version will prevail. These documents are also available free of charge at Onxeo’s registered office at 49, boulevard du Général Martial Valin – 75015 Paris and on Onxeo’s website (www.onxeo.com).

Risk Factors

Investors are invited to carefully consider the risk factors detailed in section 3 of the Universal Registration Document, section 2 of the Amendment to the Universal Registration Document and section 2 of the Securities Note. The occurrence of all or part of these risks may have an adverse effect on the Group’s business, financial position, results or ability to achieve its objectives.

On April 12, 2021 Y-mAbs Therapeutics, Inc. (the "Company" or "Y-mAbs") (Nasdaq: YMAB), a commercial-stage biopharmaceutical company focused on the development and commercialization of novel, antibody-based therapeutic products for the treatment of cancer, reported that Dr. Sebastian Chung from Memorial Sloan Kettering Cancer Center ("MSK") presented a virtual poster discussing the SADA technology platform for pre-targeted radioimmunotherapy against GPA33 in a xenograft model of colorectal peritoneal carcinomatosis at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) ("AACR") Annual Meeting on April 10, 2021 (Press release, Y-mAbs Therapeutics, APR 12, 2021, View Source [SID1234577900]).

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The SADA technology utilizes a pre-targeted payload delivery method where antibody constructs assemble in tetramers and bind to the tumor target. Unbound constructs predictably disassemble into smaller antibody fragments and are excreted through the kidneys within hours after administration. In a second infusion, a radioactive payload binds to the antibody constructs to radiate the tumor. Y-mAbs expects to submit its first IND for a SADA construct targeting GD2 in the fourth quarter of 2021.

The GPA33-SADA construct was created using the SADA technology, which was licensed by the Company from MSK and Massachusetts Institute of Technology ("MIT") in April 2020. In a xenograft model of colorectal peritoneal carcinomatosis, GPA33-SADA showed a favorable tumor to blood ratio radioactivity uptake of 122 measured 24 hours after injection. GPA33 is expressed on 95% of all colorectal cancers. An IND for the GPA33-SADA is targeted for next year.

Researchers at MSK developed GPA33-SADA, which is exclusively licensed by MSK and MIT to Y-mAbs. As a result of this licensing arrangement, both MSK and MIT have institutional financial interests related to the compound and Y-mAbs.

On April 12, 2021 Orion reported that it will publish Interim Report for January–March 2021 on Tuesday, 27 April 2021 approximately at 12.00 noon EEST (Press release, Orion , APR 12, 2021, View Source [SID1234577916]). The release and related presentation material will be available on the company’s website at www.orion.fi/en/investors after publishing.

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Webcast and conference call

A webcast and a conference call for analysts, investors and media will be held on Tuesday, 27 April 2021 at 13.30 EEST. The event will be held only online and by conference call.

A link to the live webcast will be available on Orion’s website at www.orion.fi/en/investors. A recording of the event will be available on the website later the same day.

On April 12, 2021 Transgene (Paris:TNG), a biotech company that designs and develops virus-based immunotherapeutics against cancer, reported that Management will participate in the upcoming investor events set out below (Press release, Transgene, APR 12, 2021, View Source [SID1234577933]):

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– SmallCap Event – Digital event
14 & 15 April 2021

– KEMPEN LIFE SCIENCES CONFERENCE – 2021 Thematic Virtual Series
21 April 2021 – Immuno and Targeted Oncology

– Spring European Midcap Event – Digital event
22 & 23 June 2021