On April 10, 2018 Trillium Therapeutics Inc. (Nasdaq/TSX: TRIL), a clinical stage immuno-oncology company developing innovative therapies for the treatment of cancer, reported its TTI-621 and TTI-622 clinical programs (Press release, Trillium Therapeutics, APR 10, 2018, View Source [SID1234525242]). TTI-621 and TTI-622 target CD47, a protein commonly found on the surface of cancer cells. CD47 emits a "do not eat" signal to the immune system, allowing cancer cells to evade detection.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

TTI-621 Program

TTI-621 (SIRPa-IgG1 Fc) is a decoy receptor that blocks CD47 and delivers an activating signal to effector cells such as macrophages through its IgG1 Fc region. It is being evaluated in two multi-center clinical trials using intravenous or intratumoral administration and preliminary data from both studies were reported at last year’s American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Notably, weekly infusions of TTI-621 were shown to be well tolerated and intratumoral injection was observed to reduce local lesions in 9 out of 10 patients with mycosis fungoides, a common type of cutaneous T-cell lymphoma (CTCL). Building upon these monotherapy results, Trillium has refined and focused its TTI-621 clinical program.

"Our thorough signal-seeking efforts in the TTI-621 program have successfully identified T-cell lymphoma as an indication of interest," said Dr. Niclas Stiernholm, President and CEO of Trillium Therapeutics. "Consequently, we are now moving forward with a more focused TTI-621 program that reflects our commitment to vigorously pursue this signal in both the intravenous and intratumoral trials."

Recent key modifications to the intravenous dosing study (TTI-621-01, NCT02663518) include:

Focusing near-term efforts on patients with CTCL and peripheral T-cell lymphoma (PTCL). These patients are being enrolled in separate cohorts that will be evaluated using a Simon 2-stage design, with a maximum of 35 subjects in each cohort.
Introducing a standardized intra-subject dose intensification schedule for all newly enrolled subjects to increase drug exposure.
Instituting a number of phase 2-like design elements, such as an independent data monitoring committee and central review of diagnostic pathology as well as radiographic disease imaging.
Recent key changes to the intratumoral dosing study (TTI-621-02, NCT02890368) include:

Increasing the duration of treatment to allow for weekly continuation therapy.
Ability to increase the size of each cohort from 12 to 40 patients based on early signs of clinical benefit.
Establishing new cohorts to study intratumoral TTI-621 in combination with a PD-1 or PD-L1 inhibitor, pegylated interferon-alpha 2a, talimogene laherparepvec (T-vec) or radiation therapy.
TTI-622 Program

TTI-622 (SIRPa-IgG4 Fc) is the second SIRPaFc decoy receptor that Trillium is advancing into the clinic. TTI-622 consists of the same CD47-binding domain of human SIRPa as TTI-621 but linked to an IgG4 Fc region, which has a more restricted ability to engage activating Fc receptors. It is expected to have a different pharmacologic profile than TTI-621 and is being developed primarily for combination therapy. Like TTI-621, TTI-622 has the advantage of minimal binding to human red blood cells, thereby reducing the risk of anemia and a large antigen sink effect.

"TTI-622 allows us to deepen our presence in the CD47 space," added Dr. Stiernholm. "With this agent we now have two SIRPaFc decoy receptors being evaluated in clinical trials, each with a different level of Fc receptor engagement. We are excited to compare and contrast the activity of these molecules and determine if each has unique applications that could benefit cancer patients."

A two-part, multicenter, open-label, phase 1a/1b study of TTI-622 in patients with advanced relapsed or refractory lymphoma or multiple myeloma is being initiated, with the first patient expected to be dosed in Q2 2018. In the phase 1a dose-escalation part, patients will be enrolled in sequential dose cohorts to receive TTI-622 once weekly to characterize safety, tolerability, pharmacokinetics, and to determine the maximum tolerated dose. In the phase 1b part, patients will be treated with TTI-622 in combination with rituximab, a PD-1 inhibitor or a proteasome inhibitor-containing regimen

On April 9, 2018 Otsuka Pharmaceutical Co., Ltd. reported that it has entered into an agreement with Takara Bio for co-development and exclusive sales rights in Japan for Takara’s NY-ESO-1 siTCRTM (TBI-1301, TBI-1301-A) and CD19 CAR (TBI-1501), both gene therapy products in development for cancer applications (Press release, Takara Holdings, APR 9, 2018, View Source [SID1234591489]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Under the agreement, the companies will aim for early regulatory approval for the manufacture and sale of the two therapeutic products in Japan. Takara Bio will be responsible for manufacturing and quality control of the two investigational products, while Otsuka will be responsible for clinical trials, other clinical studies, regulatory submissions, product sales and safety data collection. There are no limitations on the target indications in the agreement. Otsuka also holds a right of first refusal for nine Asian countries outside Japan.

Takara Bio will receive upfront and milestone payments from Otsuka, dependent upon the achievement of specified development targets. Takara Bio will supply Otsuka with the products based on specified financial terms. For the NY-ESO-1 siTCRTM gene therapy product, Takara Bio will receive milestone payments upon the achievement of target sales in addition to a running royalty on net sales. The upfront and milestone payments will be up to a maximum total amount of approximately 6.3 billion yen.

Toshiki Sudo, executive director, Research and Otsuka board member noted that, "We are striving to develop innovative products that contribute to the health of humankind around the world, a part of which is co-development cooperation with Takara Bio. We know from our collaboration with Takara Bio on their oncolytic virus HF10 that they have highly advanced biotechnologies and manufacturing facilities dedicated to cell therapy. We aspire jointly to advance biologics research including gene and cell therapy to satisfy currently unsatisfied medical needs."

Masanobu Kimura, Takara Bio board member and president of the Gene Therapy Business Unit, commented that the collaboration with Otsuka, which has broad experience in clinical development, pharmaceutical affairs and sales of pharmaceutical products, will contribute to the development, commercialization and value maximization of the therapeutic products. "We are convinced of further progress on the effective development, aided by the designation of NY-ESO-1・siTCRTM gene therapy product under "SAKIGAKE Designation System" (prioritized review) by the Japanese Ministry of Health, Labour and Welfare on March 27, 2018."

For more information about Takara Bio, please click here: View Source

On April 9, 2018 MorphoSys AG (FSE: MOR; Prime Standard Segment, TecDAX; OTC: MPSYY) reported that it has commenced an initial public offering in the United States of up to 8,300,000 American Depositary Shares ("ADSs") pursuant to a Registration Statement on Form F-1, as amended, filed with the U.S. Securities and Exchange Commission (Press release, MorphoSys, APR 9, 2018, View Source [SID1234556337]). Furthermore, MorphoSys expects to grant the underwriters a 30-day option to purchase additional ADSs of up to 15% of the total number of ADSs placed in the offering (i.e. up to 1,245,000 additional ADSs). Each ADS will represent 1/4 of a MorphoSys ordinary share. The new ordinary shares underlying the ADSs will be issued from MorphoSys’s authorized capital 2017-II, excluding pre-emptive rights of existing shareholders and representing up to 8.1% (including the underwriters’ option to purchase additional ADSs) of the registered share capital of MorphoSys prior to the consummation of the offering.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

The final price of the offered ADSs will be determined largely on the basis of the XETRA closing price of MorphoSys’s shares on the Frankfurt Stock Exchange on the pricing date (expected for the week of April 16, 2018) translated into U.S. dollars at the then prevailing exchange rate and using an ADS to share ratio of four to one. Application has been made to list the ADSs on the Nasdaq Global Market in the United States under the ticker symbol "MOR".

Within the United States of America, the securities referred to in this release are to be offered only by means of a prospectus. A copy of the preliminary prospectus can be obtained from Goldman Sachs & Co. LLC, Prospectus Department, 200 West Street, New York, NY 10282, telephone: 1-866-471-2526, facsimile: 1-212-902-9316 or by e-mailing [email protected]; J.P. Morgan Securities LLC, c/o Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, telephone: 1-866-803-9204; Leerink Partners LLC, Attention: Syndicate Department, One Federal Street, 37th Floor, Boston, MA 02110, by telephone at 1-800-808-7525, ext. 6132, or by e-mailing [email protected].

A Registration Statement relating to these securities has been filed with the U.S. Securities and Exchange Commission but has not yet become effective. The securities may not be sold, nor may offers to buy be accepted, prior to the time the Registration Statement becomes effective.

On 9 April 2018, RhoVac reported the board of directors resolved to propose the annual general meeting of 9 May 2018 to resolve on a rights issue of approximately SEK 24.5 million before issue costs (Press release, RhoVac, APR 9, 2018, View Source [SID1234555937]). The net proceeds of the rights issue are primarily intended to strengthen the Company’s position, thereby creating better conditions in the work of identifying potential partnerships or outsourcing opportunities. As part of this, the Company will also initiate preparations for Phase IIb clinical trials.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

Persons, who on the record date 16 May 2018 are shareholders of RhoVac, have pre-emptive rights to subscribe for new shares in the rights issue, whereby six (6) existing shares entitle to subscription for one (1) new share at a subscription price of SEK 18 per share. The subscription period runs from 18 May 2018 up to and including 1 June 2018.

The rights issue is secured up to 80 percent through subscription undertakings on approximately 6.0 MSEK equal to approximately 24.4 percent and entered guarantee undertakings on approximately 13.6 MSEK equal to approximately 55.6 percent. All the members of the Board of Directors and senior executives participate through subscription undertaking. All external investors who entered guarantee undertakings also participate through subscription undertaking.

Background and reasons

RhoVac is a biotechnology company conducting research and development of an immunotherapeutic cancer vaccine. The Company’s primary focus is the development of the drug candidate RV001 with the potential to prevent or limit the spread and recurrence of cancer in the treatment of several different cancer indications. The Company’s development strategy is based on licensing or selling all or parts of the business as soon as possible after completion of clinical phase I/II trial regarding RV001. As the ongoing phase I/II study is in its final stages, RhoVac is investing aggressively in its business development through, among other things, to, as previously announced, employ David Colpman at Colpman Consulting Ltd. The reason for the rights issue of approximately SEK 24.5 million at full subscription (before issue costs) is to primarily strengthen the business development with the purpose of identifying possible licensing opportunities or partnerships, follow-up of clinical phase I/II study, regulatory preparations for a clinical phase IIb study and general working capital required.

A fully subscribed rights issue would provide the Company with SEK 21.5 million (after issue costs), which exceeds the Company’s capital requirements over the next 12 months. In this case, the Company will adjust scheduled activities and allocation of capital taking into account the status of potential licensing and partnership discussions. Focus will be on activities that at the time are deemed most relevant in order to increase the value of the Company. In a step to further strengthen the business development in the next 12 months, the Board will propose Gunnar Gårdemyr as a new Board member at the AGM. The Company wishes to use Mr. Gårdemyr’s extensive experience and contact network in the Life Science area to further strengthen the Company’s business development.

The rights issue

On 9 April 2018, the board of directors of RhoVac AB resolved to propose the annual general meeting of 9 May 2018 to resolve on a new share issue with pre-emptive rights for the Company’s existing shareholders of approximately SEK 24.5 million before issue costs. Persons, who on the record date 16 May 2018 are shareholders of RhoVac, have pre-emptive rights to subscribe for new shares in the rights issue, whereby six (6) existing shares entitle to subscription for one (1) new share (i.e. a 1:6 subscription ratio).

The subscription price amounts to SEK 18.00 per share. The subscription period runs from and including 18 May up to and including 1 June 2018. Through the rights issue, not more than 1,360,507 new shares will be issued, corresponding to a share capital increase of SEK 244,891.26.

Subscription and guarantee undertakings

The rights issue is secured through subscription and guarantee undertakings up to 80 percent of the rights issue, corresponding to approximately SEK 19.6 million. RhoVac has received subscription undertakings of approximately SEK 6.0 million, corresponding to approximately 24.4 percent of the rights issue, from all the members of the Board of Directors and senior executives and, in particular, from a limited number of external investors by overtaking subscription rights. In addition, the Company has received guarantee undertakings of approximately SEK 13.6 million, corresponding to approximately 55.6 percent of the rights issue, whereof all of them have agreed to takeover subscription rights.

Shareholders who choose not to participate in the rights issue will have their shareholdings diluted by approximately 14.3 percent but are able to fully or partially financially compensate for this dilution by selling their subscription rights. In the event that all shares are not subscribed for with subscription rights, the board will, within the framework of the maximum amount of the rights issue, decide on the allotment of shares subscribed for without subscription rights

The rights issue is subject to approval from the annual general meeting of 9 May 2018. The convening notice of the annual general meeting is announced through a separate press release.

The full terms and conditions of the rights issue, as well as other information about the Company, will be outlined in an information memorandum, which will be published prior to the commencement of the subscription period.

Indicative timetable

9 May 2018 Annual general meeting for resolution on the rights issue
14 May 2018 Last day of trading in the RhoVac share, including the right to participate in the rights issue
16 May 2018 Record date for the right to participate with pre-emptive right in the rights issue
18 May – 1 June 2018 Subscription period
18 May – 30 May 2018 Trading in subscription rights
Around 7 June 2018 Announcement of the results of the rights issue
Advisers

Arctic Securities AS, Sweden branch, is acting as financial adviser to RhoVac in connection with the rights issue. Advokatfirman Lindahl is acting as legal adviser to the Company.

On April 9, 2018 Verastem, Inc. (NASDAQ:VSTM), a biopharmaceutical company focused on developing and commercializing medicines to improve the survival and quality of life of cancer patients, reported that the U.S. Food and Drug Administration (FDA) has accepted for filing with Priority Review its New Drug Application (NDA) for its lead product candidate duvelisib (Press release, Verastem, APR 9, 2018, View Source [SID1234529549]). Duvelisib is a first-in-class oral dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, for which Verastem is seeking full approval for the treatment of relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and accelerated approval for the treatment of relapsed or refractory follicular lymphoma (FL). The FDA target action date is October 5, 2018.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

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

                  Schedule Your 30 min Free Demo!

"Obtaining Priority Review in the U.S. for duvelisib marks another important milestone for Verastem and speaks to the unmet need in relapsed/refractory CLL/SLL and FL and the urgency to identify effective therapies to treat these patients," said Robert Forrester, President and Chief Executive Officer of Verastem. "As an orally administered therapy, we believe duvelisib will provide an important treatment option for patients with CLL/SLL and FL, and for the physicians who treat them. We look forward to working with the FDA during the review process. We are continuing our commercial preparations for duvelisib to execute the launch promptly in the U.S. if approved. In parallel, we are exploring ex-U.S. partnering opportunities for duvelisib and plan to file a European Marketing Application towards the end of the year."

Priority Review is granted by the FDA to drugs that, if approved, would provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of a serious condition. Duvelisib has received Fast Track Designation from the FDA for patients with CLL who have received at least one prior therapy and for patients with FL who have received at least two prior therapies. In addition, duvelisib received orphan drug designation in the United States and the European Union for patients with CLL, SLL and FL.

About Duvelisib

Duvelisib is a first-in-class investigational, dual inhibitor of phosphoinositide 3-kinase (PI3K)-delta and PI3K-gamma, two enzymes known to help support the growth and survival of malignant B-cells and T-cells. PI3K signaling may lead to the proliferation of malignant B- and T-cells and is thought to play a role in the formation and maintenance of the supportive tumor microenvironment.1,2,3 Duvelisib was evaluated in late- and mid-stage extension trials, including DUO, a randomized, Phase 3 monotherapy study in patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),4 and DYNAMO, a single-arm, Phase 2 monotherapy study in patients with refractory indolent non-Hodgkin lymphoma (iNHL).5 Both DUO and DYNAMO achieved their primary endpoints and the FDA is reviewing a New Drug Application (NDA) requesting the full approval of duvelisib for the treatment of patients with relapsed or refractory CLL/SLL, and accelerated approval for the treatment of patients with relapsed or refractory follicular lymphoma (FL). Duvelisib is also being developed by Verastem for the treatment of peripheral T-cell lymphoma (PTCL), which has Fast Track status, and is being investigated in combination with other agents through investigator-sponsored studies.6 Information about duvelisib clinical trials can be found on www.clinicaltrials.gov.