Fate Therapeutics Announces Day 100 Clinical Results from Phase 1 Stage of PROTECT Trial of ProTmune™ and Initiation of Phase 2 Stage

On December 11, 2017 Fate Therapeutics, Inc. (NASDAQ:FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported Day 100 clinical data from the Phase 1 stage of its PROTECT clinical trial of ProTmune, the Company’s next-generation hematopoietic cell graft for patients with hematologic malignancies (Press release, Fate Therapeutics, DEC 11, 2017, View Source [SID1234522554]). All seven subjects receiving ProTmune remained alive and relapse-free during the first 100 days following hematopoietic cell transplantation (HCT). Three of the seven subjects experienced acute graft-versus-host disease (GvHD) during the first 100 days following HCT. Each of these three subjects responded to standard-of-care steroid treatment with a median time to resolution of the maximum GvHD grade of 7 days [range: 5-8 days].

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"The significant risk of GvHD limits broad application of allogeneic transplant due to uncertainty of its short- and long-term impact on the recipient. It occurs frequently with variable intensity and can be a devastating disease when unresponsive to treatment. The requisite extended use of immunosuppressive agents to treat GvHD compromises the anti-leukemia activity of the transplant procedure and can significantly increase the risk of cancer relapse and mortality while also placing patients at risk for opportunistic infection," said Richard Maziarz, M.D., Principal Investigator, Oregon Health Sciences University. "The administration of a hematopoietic cell graft that is optimized to attenuate T-cell alloreactivity and maintain the graft’s anti-leukemia activity is a novel and highly-attractive therapeutic approach to decrease the risk and enhance the curative potential of allogeneic transplantation."

PROTECT Phase 1 Day 100 Clinical Results

Clinical data from the Phase 1 stage of PROTECT were presented today by Dr. Maziarz during a poster session at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. The Phase 1 stage included seven adult subjects with hematologic malignancies undergoing matched unrelated donor HCT following myeloablative conditioning. During the first 100 days following HCT, all seven subjects receiving ProTmune remained alive and relapse-free. Three of the seven subjects experienced acute GvHD during the first 100 days following HCT, all of whom responded to standard-of-care steroid treatment. The median time to resolution of the maximum GvHD grade was 7 days [range: 5-8 days]. There were no events of graft failure, and there were no ProTmune-related serious adverse events reported by investigators.

PROTECT Day 100 Clinical Data
Subject 1 2 3 4 5 6 7
Hematologic Malignancy MDS AML AML ALL ALL ALL AML
CD34+ cell dose (x106/kg) 10.3 4.6 10.9 4.8 3.2 3.0 9.4
CD3+ cell dose (x108/kg) 3.1 1.8 2.6 2.8 2.0 1.2 2.8
ProTmune-related SAEs None None None None None None None
Day of Neutrophil Engraftment 1 Day 14 Day 18 Day 22 Day 15 Day 16 Day 18 Day 19
Acute GvHD / Grade (CIBMTR) None None Grade 2 None Grade 2 Grade 3 None
Treatment Responsive — — Yes — Yes Yes —
Time to Resolution of Maximum Grade — — 7 days — 8 days 5 days —
Cancer Relapse-free Yes Yes Yes Yes Yes Yes Yes
Survival Yes Yes Yes Yes Yes Yes Yes
1 As measured from the day following HCT

"The Day 100 clinical results from our Phase 1 stage of PROTECT support the unique therapeutic potential of ProTmune to reduce graft-versus-host disease and promote relapse-free survival. We are very encouraged by these initial clinical findings and the potential of ProTmune to deliver transformative benefits to cancer patients," said Chris Storgard, M.D., Chief Medical Officer of Fate Therapeutics. "The randomized, controlled and double-blinded Phase 2 stage of PROTECT is enrolling subjects at 14 U.S. centers of excellence. Given the high rates of morbidity and mortality underlying hematopoietic cell transplantation, we have also engaged the FDA, under our Fast Track designation for ProTmune, to discuss the necessary activities for product registration."

All subjects receiving ProTmune in the PROTECT Phase 1 stage are being followed for a period of two years following HCT. As of a November 29, 2017 data cut-off, all subjects remained relapse-free, and there were no events of graft failure and no serious adverse events related to ProTmune reported by investigators. Non-relapse mortality was reported in two subjects (Subject 1 on Day 228; Subject 3 on Day 151). Five of seven subjects remained on study with median time on study of 154 days [Day 106 — 254].

PROTECT Phase 2 Design
The Phase 2 stage of PROTECT is a randomized, controlled and double-blinded clinical trial assessing the safety and efficacy of ProTmune in up to 60 adult subjects with hematologic malignancies undergoing matched unrelated donor HCT following myeloablative conditioning. Subjects are being randomized, in a 1:1 ratio, to receive either ProTmune or a conventional matched unrelated donor mobilized peripheral blood cell graft. The primary efficacy endpoint of PROTECT is cumulative incidence of Grades 2-4 acute GvHD by Day 100 following HCT, where prospective clinical studies have shown that 40% to 80% of patients undergoing matched unrelated donor transplant experience Grades 2-4 acute GvHD. Immunosuppressant treatments are effective in only about half of affected HCT patients and are associated with a marked increase in severe infections and cancer relapse. Additional endpoints, such as rates of cancer relapse, chronic GvHD, non-relapse mortality and overall survival, are also being assessed. Fourteen U.S. centers are currently open for enrollment in the Phase 2 stage of PROTECT.

About Acute GvHD
Acute graft-versus-host disease (GvHD) is a severe immunological disease that commonly arises in patients during the first weeks following allogeneic HCT when newly-transplanted donor immune cells attack the patient’s tissues and organs, resulting in a potentially fatal immune system reaction. Prospective clinical studies have shown that 40% to 80% of patients undergoing matched unrelated donor transplant experience Grades 2-4 acute GvHD, with most incidents occurring by Day 60 following HCT despite the use of standard prophylaxis regimens. The disease is the leading cause of early morbidity and mortality in matched unrelated donor transplant, where death directly attributable to acute GvHD or its treatment occurs in 10% to 20% of patients. There are currently no FDA-approved preventive therapies and very few treatment options for acute GvHD.

About ProTmune
ProTmune is an investigational next-generation hematopoietic cell graft for the prevention of acute graft-versus-host disease (GvHD) in patients undergoing allogeneic hematopoietic cell transplantation. ProTmune is manufactured by pharmacologically modulating a donor-sourced, mobilized peripheral blood graft ex vivo with two small molecules (FT1050 and FT4145) to decrease the morbidity and mortality of acute GvHD while maintaining the anti-leukemia activity of the graft. ProTmune has been granted Orphan Drug and Fast Track Designations by the U.S. Food and Drug Administration, and Orphan Medicinal Product Designation by the European Commission.

Daiichi Sankyo Presents Phase 1 Data for EZH1/2 Dual Inhibitor DS-3201 in Patients with Non-Hodgkin Lymphomas at the 59th Annual Meeting of the American Society of Hematology

On December 11, 2017 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported that preliminary safety and efficacy data from a phase 1 study of DS-3201, an investigational and potential first-in-class EZH1/2 dual inhibitor, in patients with relapsed or refractory non-Hodgkin lymphomas (NHLs) were presented during a poster session at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta, Georgia (Press release, Daiichi Sankyo, DEC 11, 2017, View Source [SID1234522553]).

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Preliminary exploratory efficacy results from an ongoing phase 1 dose escalation study showed that an overall response rate of 58.8 percent (10 of 17 patients) was observed with single agent DS-3201 in 17 evaluable patients with NHLs, including B-cell and T-cell lymphomas, who were relapsed from or refractory to standard treatment or for whom no standard treatment was available. Among the 10 patients with response, there were one complete remission and nine partial remissions. Additionally, four patients experienced stable disease and three patients experienced progressive disease.

An overall response rate of 45.5 percent (5 of 11 patients) was observed with DS-3201 in 11 evaluable patients with B-cell lymphomas, including follicular lymphoma (5 patients), diffuse large B-cell lymphoma (3 patients), extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (2 patients) and lymphoplasmacytic lymphoma (1 patient). An overall response rate of 83.3 percent (5 of 6 patients) was observed with DS-3201 in six evaluable patients with T-cell lymphomas, including peripheral T-cell lymphoma not otherwise specified (2 patients), angioimmunoblastic T-cell lymphoma (2 patients) and adult T-cell leukemia-lymphoma (2 patients).

"Based on these preliminary safety and efficacy data on DS-3201 in a clinical setting, further evaluation of DS-3201 is warranted," said Dai Maruyama, MD, PhD, Department of Hematology, National Cancer Center Hospital, Tokyo, Japan. "As the first dual inhibitor of EZH1 and EZH2 in clinical development, DS-3201 may represent a new epigenetic approach to treating blood cancers. We look forward to reviewing additional data as it becomes available to evaluate the potential of this approach."

Following observation of dose-limiting toxicities (DLTs) in three of 18 evaluable patients, dose expansion is ongoing to determine a conclusive recommended phase 2 dose. Four DLTs were observed in three patients who received either the 200 mg or 300 mg dose: there were three cases of temporary grade 4 platelet count decreases (one patient in the 200 mg cohort and two patients in the 300 mg cohort) and one case of grade 3 anemia requiring transfusion in a patient in the 300 mg cohort. Preliminary safety data from 18 evaluable patients in the study also were reported. The most common treatment emergent hematologic adverse events of any grade seen in all patients included decreased platelet count (77.8 percent), anemia (55.6 percent), decreased lymphocyte count (50.0 percent) and decreased neutrophil count (44.4 percent). The most common treatment emergent non-hematologic adverse events were dysgeusia (50.0 percent), alopecia (33.3 percent), diarrhea (22.2 percent), decreased appetite (22.2 percent), nasopharyngitis (22.2 percent), alanine aminotransferase increased (22.2 percent), rash (16.7 percent), aspartate aminotransferase increased (16.7 percent) and dry skin (16.7 percent). One serious adverse event of grade 3 pneumocystis jirovecii pneumonia (PJP) led to discontinuation from the study.There was one additional non-serious case of PJP observed, leading to the institution of prophylactic treatment for all subsequent patients enrolled into the study.

DS-3201 targets epigenetic regulation by inhibiting both the EZH1 (enhancer of zeste homolog 1) and EZH2 (enhancer of zeste homolog 2) enzymes, which may reactivate various genes that have been silenced by the protein H3K27me3.1 Reactivation of the silenced genes has been shown to result in decreased proliferation of EZH2-expressing cancer cells. Preclinical research has shown that DS-3201 suppressed trimethylation of H3K27 in cells (IC50: 0.55 nM) more potently than EZH2 selective inhibitors.1

"Targeting epigenetic regulation is an approach to treating cancer that aims to reverse aberrant epigenetic changes that contribute to cancer cell growth and to maintain normal gene expression. The dual inhibition of EZH1/2 is theoretically able to provide a different spectrum of activity compared to EZH2-specific inhibitors already in the clinic. Our phase 1 program is designed to address the question of the potential benefit for this dual mode of action," said Antoine Yver, MD, MSc, Executive Vice President and Global Head, Oncology Research and Development, Daiichi Sankyo. "In addition to the phase 1 study in non-Hodgkin lymphomas, we also are evaluating targeting epigenetic regulation with DS-3201 in patients with acute myeloid leukemia and acute lymphocytic leukemia."

About Non-Hodgkin Lymphoma
Non-Hodgkin lymphoma (NHL) is a form of cancer that originates in lymphocytes, a type of white blood cell.2 The two main types of NHL are B-cell lymphomas and T-cell lymphomas, which are classified into subtypes based on the origin and stage of the cancer.2 There were an estimated 386,000 new cases and about 200,000 deaths globally from NHL in 2012.3 In Japan, there were nearly 21,000 new cases of NHL in 2012, accounting for around five percent of cases worldwide.3 While recent treatment advances have led to improved outcomes for patients with certain types of NHL, patients with aggressive NHL subtypes or relapsed or refractory disease still face a poor prognosis.2,4

About the DS-3201 Phase 1 Study
A multicenter, non-randomized, open-label phase 1 dose escalation trial in Japan is enrolling adult patients with non-Hodgkin lymphomas (NHL) who have relapsed from or are refractory to standard treatment or for whom no standard treatment is available. The primary objectives are to evaluate the safety and pharmacokinetics of multiple-dose monotherapy of DS-3201 and to determine the recommended phase 2 dose. Secondary objectives are to determine the maximum tolerated dose of DS-3201 and to conduct exploratory evaluations of DS-3201-related biomarkers and the efficacy of DS-3201. For more information about the clinical trial, visit ClinicalTrials.gov.

About DS-3201
Part of the AML Franchise of the Daiichi Sankyo Cancer Enterprise, DS-3201 is an investigational and potential first-in-class EZH1/2 dual inhibitor in phase 1 clinical development for hematologic cancers including acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL) and non-Hodgkin lymphoma (NHL). DS-3201 is an investigational agent that has not been approved by the FDA or any other regulatory agency worldwide as a treatment for any indication. Safety and efficacy have not been established.

About Daiichi Sankyo Cancer Enterprise
The vision of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking in order 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 Antibody Drug Conjugate (ADC) and Acute Myeloid Leukemia (AML) Franchises, our cancer pipeline includes more than 20 small molecules, monoclonal antibodies and ADCs stemming from our powerful research engines: our two laboratories for biologic/immuno-oncology and small molecules in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in Berkeley, CA. Compounds in development include: quizartinib, an oral FLT3 inhibitor, for newly-diagnosed and relapsed or refractory AML with FLT3-ITD mutations; DS-8201, an ADC for HER2-expressing breast and gastric cancer, and other HER2-expressing solid tumors; and pexidartinib, an oral CSF-1R inhibitor, for tenosynovial giant cell tumor (TGCT), which is also being explored in a range of solid tumors in combination with the anti-PD1 immunotherapy pembrolizumab.

Kura Oncology Identifies Potential Biomarkers of Activity for Lead Candidate Tipifarnib in Bone Marrow Cancers

On December 11, 2017 Kura Oncology, Inc. (Nasdaq:KURA), a clinical-stage biopharmaceutical company focused on the development of precision medicines for oncology, today reported new findings supporting the development of lead candidate tipifarnib, a potent and selective inhibitor of farnesyl transferase, in the treatment of certain bone marrow cancers (Press release, Fate Therapeutics, DEC 11, 2017, View Source;p=RssLanding&cat=news&id=2322103 [SID1234522555]). These results were featured in presentations at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Atlanta. Copies of the posters are now available on the company’s website at www.kuraoncology.com.

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Among the findings presented at ASH (Free ASH Whitepaper) were the identification of CXCR4/CXCR2 expression ratio and bone marrow homing of myeloid cells as potential biomarkers of tipifarnib activity across the bone marrow cancers, myelodysplastic syndromes (MDS), acute myeloid leukemia (AML) and chronic myelomonocytic leukemia (CMML), further showing that the CXCL12/CXCR4 pathway is a potential therapeutic target of farnesyl transferase inhibitors.

"Although tipifarnib has previously demonstrated clinical responses in certain patients with AML and MDS, no molecular mechanism of action was identified that could explain the activity of the drug candidate in those patient populations," said Troy Wilson, Ph.D., J.D., President and Chief Executive Officer of Kura Oncology. "These new findings are exciting because they may define potential biomarkers for tipifarnib in bone marrow tumors and characterize a subgroup of patients that are most likely to derive clinical benefit from a targeted therapy such as tipifarnib."

Previously, Kura Oncology reported preliminary results from an ongoing Phase 2 clinical trial of tipifarnib in patients with peripheral T-cell lymphoma (PTCL) identifying the CXCL12/CXCR4 pathway as a potential target of tipifarnib. Specifically, high levels of CXCL12 gene expression and absence of single nucleotide gene variations in the 3′-untranslated region of the CXCL12 gene were associated with observed clinical activity of tipifarnib in these PTCL patients.

In the ASH (Free ASH Whitepaper) presentation entitled, "The CXCL12/CXCR4 Pathway As a Potential Target of Tipifarnib: Preliminary Results from an Open-Label, Phase II Study in Relapsed or Refractory Peripheral T-Cell Lymphoma," Kura Oncology extends these observations and provides data supporting the observed tipifarnib-derived clinical benefit for the CXCL12-positive population.

CXCL12 is a chemokine that is secreted in large amounts by lymph nodes, bone marrow stroma, liver, and lung, and plays key roles in tumor invasion, bone marrow homing and site of metastasis. Among its multiple functions, CXCL12 is essential for homing of myeloid cells to the bone marrow and lymphoid cells to lymph nodes and other organs.

Based on its initial observations in PTCL, the company investigated a role for the CXCL12/CXCR4 pathway and bone marrow homing of myeloid cells as biomarkers of tipifarnib activity in AML and MDS studies.

In the ASH (Free ASH Whitepaper) presentation entitled, "The CXCL12/CXCR4 Pathway As a Potential Target of Tipifarnib in Acute Myeloid Leukemia and Myelodysplastic Syndromes," Kura Oncology presented results that identify the ratio of CXCR4/CXCR2 gene expression and bone marrow homing of myeloid cells as potential biomarkers of the activity of tipifarnib in certain bone marrow tumors. The results were obtained by analyzing data from previous studies of tipifarnib in AML and MDS, as well as data from the ongoing Phase 2 clinical trial of tipifarnib in CMML.

"We were very encouraged to identify CXCR4/CXCR2 expression ratio and bone marrow homing as markers of tipifarnib’s activity in MDS, AML and CMML," said Antonio Gualberto, M.D., Ph.D., Chief Medical Officer at Kura Oncology. "Although our analysis is retrospective, the fact that we observe a consistent clinical benefit across different endpoints, treatment settings and indications gives us increased confidence in the potential for these biomarkers. Based on our preliminary data, we believe CXCL12/CXCR4 may have the potential to unlock the therapeutic value of farnesyl transferase inhibition across multiple bone marrow neoplasias."

About Tipifarnib

Kura Oncology’s lead candidate, tipifarnib, is a potent and selective inhibitor of the enzyme farnesyl transferase, a key cell signaling process implicated in cancer initiation and development. Tipifarnib has previously been studied in more than 5,000 patients in more than 70 clinical trials has a well-established safety profile and has demonstrated compelling and durable anti-cancer activity in certain patient subsets.

Leveraging advances in next-generation sequencing as well as emerging information about cancer genetics and tumor biology, Kura Oncology is seeking to identify patients most likely to benefit from tipifarnib. The company is conducting clinical and preclinical studies in multiple disease indications where tipifarnib has previously shown signs of activity with the goal of identifying and validating biomarkers associated with the observed clinical activity of tipifarnib.

In September 2017, Kura Oncology reported that its Phase 2 trial of tipifarnib in patients with HRAS mutant head and neck squamous cell carcinomas (HNSCC) achieved its primary efficacy endpoint prior to the completion of patient enrollment. The company is now planning to initiate a registration-enabling study of tipifarnib in HRAS mutant HNSCC in 2018.

Phase 1 Data for Flotetuzumab, MacroGenics’ CD123 x CD3 DART® Molecule, Presented at 59th Annual ASH Meeting

On December 11, 2017 MacroGenics, Inc. (NASDAQ:MGNX), a clinical-stage biopharmaceutical company focused on discovering and developing innovative monoclonal antibody-based therapeutics for the treatment of cancer, as well as autoimmune disorders and infectious diseases, reported the presentation of clinical data from its ongoing Phase 1 study of flotetuzumab in an oral session at the 59th Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) in Atlanta, Georgia (Press release, MacroGenics, DEC 11, 2017, View Source [SID1234522556]). John E. Godwin, M.D., Program Leader, Hematologic Malignancies at Earle A. Chiles Research Institute at Providence Cancer Center in Portland, Oregon presented "Preliminary Results of a Phase 1 Study of Flotetuzumab, a CD123 x CD3 Bispecific DART Protein, in Patients with Relapsed/Refractory Acute Myeloid Leukemia and Myelodysplastic Syndrome."

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The ongoing Phase 1, first-in-human study of flotetuzumab was designed to determine safety, tolerability, maximum tolerated dose and initial anti-leukemic activity in patients with relapsed or refractory acute myeloid leukemia (AML) or intermediate-2/high risk myelodysplastic syndrome (MDS). To date, a total of 57 patients have been enrolled, including 11 AML patients in the dose expansion cohort.

Consistent with the dose escalation data that was previously presented at ESMO (Free ESMO Whitepaper) Congress 2017 in September, flotetuzumab has continued to demonstrate acceptable tolerability in patients treated to date in the dose expansion cohort. Infusion-related reaction and cytokine release syndrome (CRS) were the most common adverse events observed, with Grade 3 CRS occurring in 9 of 57 patients (15.8%). Implementation of a two-step, lead-in dose as well as early intervention with anti-cytokine therapy has helped to limit the severity and incidence of CRS.

As of the data cut-off date, of the eight evaluable patients in the dose expansion cohort who received a lead-in dose followed by 500 ng/kg/day of flotetuzumab via continuous IV infusion, six patients (75%) have evidence of anti-leukemic activity, with three of these patients experiencing an objective response. This included two patients who experienced CR/CRi and one patient who achieved MLF (morphologic leukemia-free state).

The duration of response for the eight patients who have achieved a MLF, CRi or CR in the dose escalation and dose expansion cohorts ranged from 1.0 to 5.8 months, with five of these responses still ongoing as of the November 30, 2017 data cut-off.

Further, in a translational data poster presentation, MacroGenics also described studies that support a rationale for using checkpoint blockade as an approach to potentially enhance the anti-leukemic activity of flotetuzumab. Among these findings, modulation of the PD-1/PD-L1 pathway was observed in patients treated with flotetuzumab, and the combination of flotetuzumab and PD-1/PD-L1 inhibitors was shown to synergistically enhance T-cell mediated cytotoxicity against AML cell lines in vitro.

"We continue to be encouraged by the tolerability and anti-leukemic activity of flotetuzumab as well as by the early data regarding the durability of responses observed in patients from our ongoing Phase 1 study of flotetuzumab," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "In addition, given the data-supported rationale for combining flotetuzumab with anti-PD-1, we intend to initiate a combination study with the anti-PD-1 mAb, MGA012, in the coming months, while we continue to enroll the AML and MDS dose expansion cohorts. We look forward to sharing additional flotetuzumab clinical data in 2018."

The presentation at the 59th Annual ASH (Free ASH Whitepaper) meeting is available for download from the Events & Presentations page on MacroGenics’ website at View Source

About Flotetuzumab

Flotetuzumab (also known as MGD006 and S80880) is a clinical-stage molecule that recognizes both CD123 and CD3. CD123, the Interleukin-3 receptor alpha chain, has been reported to be over-expressed on cancer cells in a wide range of hematological malignancies, including AML and MDS. The primary mechanism of action of flotetuzumab is believed to be its ability to redirect T lymphocytes to kill CD123-expressing cells. To achieve this, the DART molecule combines a portion of an antibody recognizing CD3, an activating molecule expressed by T cells, with an arm that recognizes CD123 on the target cancer cells.

Flotetuzumab is currently being evaluated at 13 clinical sites in the U.S. and Europe in a Phase 1 study designed to assess the safety, tolerability, maximum tolerated dose and initial anti-leukemic activity of the molecule in patients with relapsed/refractory AML or intermediate-2/high risk MDS. MacroGenics retains full development and commercialization rights to flotetuzumab in the U.S., Canada, Mexico, Japan, South Korea and India. Servier participates in the development of flotetuzumab and has exclusive rights to this molecule in all other countries. The U.S. Food and Drug Administration has granted orphan drug designation to flotetuzumab for the treatment of AML.

ImmunoPrecise to Acquire ModiQuest Research BV

On December 11, 2017 IMMUNOPRECISE ANTIBODIES LTD. (the "Company") (TSX VENTURE: IPA)(OTC PINK: IPATF) reported that it has signed a binding letter of intent with ModiQuest Research BV ("ModiQuest") whereby the Company has agreed to acquire all of the issued and outstanding shares of ModiQuest (the "Transaction") (Press release, ModiQuest Therapeutics, DEC 11, 2017, View Source [SID1234522558]).

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The Transaction continues to realize on the Board’s commitment to grow globally through strategic acquisitions. It allows IPA to become a single source provider of services across the full antibody discovery value chain (antigen design, hit generation, lead selection, lead optimization and lead characterization) and to offer the full spectrum of antibody production methodologies (library based technologies, hybridoma methods, transgenic animal based platforms and single B cell based technology). Furthermore, the acquisition enhances the Company’s capacity for generating human antibodies.

"In acquiring ModiQuest Research B.V., IPA becomes a leading integrated antibody solutions company with global reach," said Dr. James Kuo, Chairman, Interim President of the Company.

ModiQuest

ModiQuest is a privately held company based in Oss, The Netherlands that specializes in the generation of monoclonal antibodies against difficult target antigens. ModiQuest applies proprietary technologies to all aspects of the antibody discovery process in research and development, diagnostic and therapeutic applications. Using its proprietary ModiFuse (hybridoma electrofusion), ModiSelect (B-cell selection) and ModiPhage (phage display) technologies, ModiQuest can generate very large panels of monoclonal antibodies from various backgrounds including mouse, rat, rabbit, chicken, llama and human, as well as transgenic animals harboring the human antibody gene repertoire. ModiQuest serves clients in Europe, the US, Asia and Russia. During its year-ended 2016, ModiQuest had revenues of €2,009,374 (CAD $3,037,249) and earnings of €671,799 (CAD $1,015,451).

The Transaction is accretive in both revenue and earnings and brings additional scientific and management capacity.

Terms of Transaction with ModiQuest

Under the binding letter of intent, the Company and ModiQuest have agreed to negotiate a definitive agreement (the "Definitive Agreement") whereby the Company will acquire all of the issued and outstanding shares of ModiQuest for €7,000,000 (CAD$10,570,000) (the "Purchase Price"), of which (A) €2,500,000 (CAD$3,775,000) will be paid in cash on closing, (B) €2,500,000 (CAD$3,775,000) will be satisfied by the issuance of approximately 6,622,807 common shares of the Company on closing, and (C) €2,000,000 (CAD$3,020,000) in deferred payments over a three year period (the "Deferred Payments"). The Deferred Payments will be made in three equal installments of cash and equity totaling €666,666 (CAD$1,006,665) on each anniversary date following closing of the transaction. The Deferred Payments will be prorated if the EBITDA of ModiQuest fails to equal the average EBITDA from the previous two years. ImmunoPrecise expects to finance the cash portion of the purchase price using a convertible debt instrument.

The letter of intent also requires that Jos Raats, a principal of ModiQuest, to enter into a three year management contract, which will include non-solicitation and non-competition clauses, and Mr. Raats will provide a minimum of 60% of full time employment to ModiQuest under the management contract. The Company has also agreed to appoint one of the principal shareholders of ModiQuest to its board of directors.

The parties will be entitled to carry out due diligence of each other until February 15, 2018. Upon the parties completing due diligence to their reasonable satisfaction, the parties will enter into the Definitive Agreement setting forth the terms and conditions of the Transaction by February 28, 2018. Completion of any transaction with ModiQuest is subject to a number of conditions, including but not limited to, completion of due diligence, negotiation of definitive agreements in respect of such a transaction, the availability of financing on terms acceptable to the Company, and receipt of any required regulatory and shareholder approvals. A transaction cannot be completed until these conditions are satisfied, and there can be no assurance that a transaction will be completed at all.