On November 14, 2019 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported the presentation of interim clinical data from its ongoing Phase 1 clinical trial evaluating TK216, a first-in-class, targeted, investigational small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins, in patients with relapsed or refractory Ewing sarcoma (Press release, Oncternal Therapeutics, NOV 14, 2019, View Source [SID1234551319]). Paul A. Meyers, M.D., Chief, Pediatric Sarcoma Service and Vice Chair for Clinical Affairs of Memorial Sloan Kettering Cancer Center, reported at the Connective Tissue Oncology Society (CTOS) 2019 Annual Meeting in Tokyo, Japan that one of two patients treated in the current, highest exposure dose cohort of Study TK216-01 is without evidence of Ewing sarcoma after eight months on study, and has tolerated treatments with TK216 alone or combined with vincristine well.

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"We are encouraged by this first reported deep and sustained clinical response to TK216 in a patient with Ewing sarcoma in the dose-finding portion of our clinical trial and look forward to further evaluating the recommended Phase 2 dose regimen of TK216 in a larger number of patients with this devastating disease," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "This first-in-class investigational agent may also be applicable in other malignancies driven by ETS alterations including AML and prostate cancer, which we continue to explore in preclinical studies."

Study TK216-01, Oncternal’s ongoing Phase 1 study of TK216 in patients with relapsed or refractory Ewing sarcoma, is a first-in-human, multicenter clinical trial. Trial objectives include the evaluation of safety, tolerability, pharmacokinetics and tumor response. Thirty-two patients have been treated in the dose-finding part of the trial. Patients entering the trial had previously been treated with a median of four, and up to nine prior lines of systemic therapy. TK216 has been generally well tolerated in this trial, with common side effects including myelosuppression, fatigue, nausea and alopecia. The maximum tolerated dose has been identified as 220 mg/m2/day for a seven-day treatment regimen, and 200 mg/m2/day for a 10-day regimen. Dose limiting toxicities consisted of transient and manageable myelosuppression, primarily neutropenia. No unexpected off-target toxicities have been observed.

One of two patients treated at the current, highest exposure dose regimen (200 mg/m2/day for 14 days) has experienced a deep and sustained clinical response to TK216. Multiple lung nodules regressed following two cycles of TK216 alone. After six months of treatment that included concomitant vincristine starting in the third cycle, a single 7 mm lung nodule was resected, resulting in a surgical complete remission. The patient remains with no evidence of disease after eight months of treatment. TK216, with or without vincristine, has been well tolerated by this patient, with only minimal myelosuppression. Clinical pharmacology data suggest that this dosing regimen may result in drug levels that meet or exceed those that killed tumor cells in vitro and inhibited tumor growth in animal models.

Enrollment of the final dose-finding cohort of the study is nearing completion, after which Oncternal intends to begin enrolling patients using the recommended Phase 2 dosing regimen in an expansion cohort to further evaluate the clinical response to treatment.

"I am encouraged by the depth and duration of response to TK216 in this heavily pre-treated patient with Ewing sarcoma, and that the patient tolerated his treatments with TK216 and vincristine well," said Dr. Meyers. "Advanced, refractory Ewing sarcoma is a serious and devastating condition, and novel therapies are desperately needed. These interim results of Study TK216-01, along with evolving preclinical data, suggest that this agent warrants further clinical testing in Ewing sarcoma as well as in other cancer indications."

About TK216

TK216 is an investigational, potentially first-in-class, targeted small-molecule inhibitor of the E26 transformation-specific (ETS) family of oncoproteins including fusion proteins. Tumorigenic fusion proteins involving the EWS protein and an ETS protein can be found in most cases of Ewing sarcoma. ETS-related translocations or overexpression are also found in many other tumors such as prostate cancer and acute myeloid leukemia (AML). TK216 was developed based on discoveries in the laboratory of Jeffrey Toretsky, M.D., at Georgetown Lombardi Comprehensive Cancer Center, who discovered inhibitors of EWS-FLI1 using a novel chemical screening assay. In preclinical models, TK216 was observed to bind to EWS-FLI1, blocking the interaction between this fusion protein and other transcriptome proteins such as RNA helicase A, leading to tumor cell apoptosis and inhibiting tumor growth in animal models. The U.S. Food and Drug Administration (FDA) has granted Orphan Designation and Fast Track designation to TK216 for the treatment of Ewing sarcoma. TK216 is an investigational medication that has not been approved by the FDA for any indication.

About the Study

TK216 is being evaluated in a Phase 1 clinical study as a single agent and in combination with vincristine in patients with relapsed or refractory Ewing sarcoma, a rare pediatric cancer with no standard treatment available after first-line chemotherapy. The dose-finding portion of the study is nearing completion, after which Oncternal intends to begin enrolling patients in an expansion cohort to evaluate the clinical response of treatment with TK216 in combination with vincristine using the recommended Phase 2 dosing regimen. This multi-center study is actively enrolling patients at seven clinical trial centers across the U.S. Additional information about the TK216 study may be accessed at ClinicalTrials.gov (NCT02657005).

On November 14, 2019 Leap Therapeutics, Inc. (NASDAQ:LPTX) reported financial results for the third quarter ended September 30, 2019 (Press release, Leap Therapeutics, NOV 14, 2019, View Source [SID1234551338]).

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"The body of clinical data we presented in the third quarter for both DKN-01 monotherapy and combination treatment for cancer patients continues to demonstrate impressive activity. Patients with advanced gastroesophageal junction and gastric cancer whose tumors expressed high levels of DKK1 (DKK1-high) achieved higher survival and objective response outcomes to the combination of DKN-01 and KEYTRUDA," commented Christopher K. Mirabelli, Ph.D., President and Chief Executive Officer of Leap. "DKN-01 also showed durable benefit in patients with endometrial cancer with Wnt pathway alterations, including a monotherapy complete response, highlighting the potential utility of DKN-01 for biomarker-targeted patient populations."

Dr. Mirabelli continued: "We also completed enrollment in the dose escalation phase of our clinical trial evaluating TRX518 in combination with BAVENCIO and cyclophosphamide; however, we’ve made the strategic decision to deprioritize further development of TRX518 at this time in order to focus our resources on our more advanced DKN-01 program. The safety profile observed to date was acceptable, and patients who are benefiting from treatment in the TRX518 program will continue to be treated."

DKN-01 Development Program Update

DKN-01 in ESOPHAGOGASTRIC CANCER: Leap presented data from the KEYNOTE-731 clinical study evaluating DKN-01 in combination with KEYTRUDA (pembrolizumab) in patients with advanced esophagogastric cancer. Study results demonstrated that patients with DKK1-high status had improved outcomes, including longer progression free survival (PFS) independent of PD-L1 Combined Positive Scores (CPS). In ten evaluable gastroesophageal junction and gastric cancer patients who had not received prior PD-1/PD-L1 therapy, DKK1-high patients experienced 22.1 weeks median progression free survival (PFS) and 31.6 weeks median overall survival (OS), with a 50% overall response rate (ORR) and 80% disease control rate (DCR). Fifteen evaluable DKK1-low patients experienced 5.9 weeks PFS and 17.4 weeks OS, with a 20% DCR. PD-L1 CPS did not predict efficacy to the combination of DKN-01 plus KEYTRUDA.
DKN-01 in GYNECOLOGICAL CANCERS: The Company presented data from the ongoing clinical study of DKN-01 as a monotherapy and in combination with paclitaxel in patients with advanced gynecological cancers at the International Gynecologic Cancer Society Annual Global Meeting held in September. In the cohort of sixteen evaluable monotherapy patients with epithelial endometrial cancer (EEC) with identified Wnt signaling mutations, patients had higher response rates and demonstrated longer PFS as compared to patients without Wnt signaling mutations. Specifically, one patient had a complete response and one patient had a partial response, representing a 12.5% single agent ORR, seven patients had a best response of stable disease, and seven patients had progressive disease. In the six evaluable monotherapy EEC patients who did not have any identified Wnt signaling mutations, none had clinical benefit. Patient follow-up is continuing in this study, which has been expanded to include focused cohorts of patients with carcinosarcoma.
DKN-01 plus OPDIVO in BILIARY TRACT CANCER: The first patients have been dosed in an investigator-initiated clinical study to evaluate DKN-01 in combination with Bristol-Myers Squibb’s OPDIVO (nivolumab) in previously treated patients with advanced biliary tract cancer. The study is being conducted by Massachusetts General Hospital and will enroll up to 36 biliary tract cancer patients who have progressed after one or more lines of systemic therapy for advanced biliary tract cancer. The primary endpoint of the study will be ORR, to be assessed in the overall population as well as in subgroups stratified by tumor DKK1 and PD-L1 expression. Bristol-Myers Squibb is providing OPDIVO drug supply and partial funding for the study, with Leap providing DKN-01 drug supply as well as additional partial funding.
TRX518 Development Program Update

FURTHER DEVELOPMENT OF TRX518 HAS BEEN DEPRIORITIZED: Leap has completed enrollment in dose escalation phase of the clinical trial evaluating TRX518 in combination with cyclophosphamide chemotherapy and BAVENCIO (avelumab). However, instead of pursuing additional enrollment through the expansion cohorts in this study as initially planned, the Company has decided to reprioritize resources on the further development of the DKN-01 program. There were no safety or efficacy concerns leading to this decision, and patients who are benefitting from the combination therapy will continue to be treated in the study.
Selected Third Quarter 2019 Financial Results

Net loss was $7.9 million for the third quarter 2019, compared to $6.6 million for the same period in 2018. This increase was primarily due to the recording of a $1.8 million gain in the third quarter 2018 as a result of a change in the fair value of the warrant liability, partially offset by a decrease in research and development expense.

Research and development expenses were $5.8 million for the third quarter 2019, compared to $6.5 million for the same period in 2018. This decrease was primarily due to a decrease of $0.4 million in clinical trial costs as a result of the timing of patient enrollment and a decrease of $0.3 million in manufacturing costs related to clinical trial material manufacturing campaigns.

General and administrative expenses were $2.2 million for the third quarter 2019, compared to $2.1 million for the same period in 2018. The increase was primarily due to a $0.1 million increase in stock based compensation as a result of new stock options granted to employees and directors in 2019.

Cash, cash equivalents and marketable securities totaled $10.1 million at September 30, 2019. Research and development incentive receivables, short term, totaled approximately $752,000 at September 30, 2019.

On November 13, 2019 Applied DNA Sciences, Inc. (NASDAQ: APDN) ("Applied DNA" or the "Company") a leader in Polymerase Chain Reaction (PCR)-based DNA manufacturing for product authenticity, traceability solutions and nucleic acid-based biotherapeutic research, reported the pricing of an underwritten public offering of 2,285,000 shares of its common stock and warrants to purchase up to an aggregate of 2,285,000 shares of common stock (Press release, Applied DNA Sciences, NOV 13, 2019, View Source [SID1234551131]). Each share of common stock is being sold together with one warrant to purchase one share of common stock at a combined effective price to the public of $5.25 per share and accompanying warrant. Gross proceeds, before underwriting discounts and commissions and estimated offering expenses, are expected to be approximately $12.0 million, not including any amounts received upon exercise of the warrants.

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The warrants will be immediately exercisable at a price of $5.25 per share of common stock and will expire five years from the date of issuance. The shares of common stock and the accompanying warrants, can only be purchased together in the offering, but will be issued separately. The offering is expected to close on or about November 15, 2019, subject to customary closing conditions.

Maxim Group LLC is acting as the book-running manager and Joseph Gunnar & Co. LLC is acting as a co-manager in connection with the offering.

Applied DNA has granted the underwriters a 45-day option to purchase up to an additional 342,750 shares of common stock and/or warrants to purchase up to 342,750 shares of common stock, at the public offering price less discounts and commissions.

The Securities and Exchange Commission (the "SEC") declared effective a registration statement on Form S-1 (File No. 333-233830) relating to these securities on November 13, 2019. A final prospectus relating to the offering will be filed with the SEC and will be available on the SEC’s website at View Source The offering is being made only by means of a prospectus forming part of the effective registration statement. Electronic copies of the prospectus relating to this offering, when available, may be obtained from Maxim Group LLC, 405 Lexington Avenue, 2nd Floor, New York, NY 10174, at (212) 895-3745. Before investing in this offering, interested parties should read in its entirety the registration statement that the Company has filed with the SEC, which provides additional information about the Company and this offering.

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

On November 13, 2019 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH) reported preliminary data from the ongoing Phase 1 study of DCC-3014, an oral inhibitor of CSF1R, including initial data in diffuse-type tenosynovial giant cell tumor (TGCT) patients as well as an encore presentation of the INVICTUS pivotal Phase 3 study of ripretinib, a broad-spectrum KIT and PDGFRα inhibitor, in patients with advanced gastrointestinal stromal tumors (GIST) (Press release, Deciphera Pharmaceuticals, NOV 13, 2019, View Source [SID1234551148]). Results from these programs will be presented at the Connective Tissue Oncology Society (CTOS) 2019 Annual Meeting being held November 13-16 in Tokyo, Japan.

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"We are excited to share preliminary data from the initial TGCT patients enrolled in the ongoing Phase 1 study of DCC-3014. While this program in TGCT is in its early stages, we are encouraged by the preliminary evidence of anti-tumor activity and emerging tolerability profile," said Matthew L. Sherman, M.D., Executive Vice President and Chief Medical Officer of Deciphera. "We plan to continue to enroll TGCT patients to further explore the potential of DCC-3014, with the goal of making a meaningful impact on disease progression and, importantly, quality of life for patients with TGCT."

Preliminary Data from DCC-3014 in Initial TGCT Patients

The Company’s Phase 1 study of DCC-3014 was designed to evaluate the safety, pharmacokinetics, and pharmacodynamics of multiple doses of DCC-3014 in patients with advanced solid tumors and TGCT. Tumor reductions from baseline were determined by investigator assessment by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The CTOS presentation highlights preliminary results from the initial three TGCT patients enrolled in the dose-escalation portion of the Phase 1 study. Safety, pharmacokinetic, and pharmacodynamic data were analyzed as of September 10, 2019, with additional anti-tumor activity data reported as of November 8, 2019.

All three patients with diffuse-type TGCT treated as of the data analyses dates showed preliminary anti-tumor activity.
As of their first tumor assessment at Cycle 3 Day 1, tumor reductions from baseline of 48%, 25% and 24%, respectively, were observed.
One patient had a confirmed partial response, which has been sustained for nine months and is ongoing as of the most recent investigator report, with a tumor reduction from baseline of 84% as of Cycle 10 Day 1.
Symptomatic improvements in mobility and reduced pain, as reported by the investigator, were observed.
These patients were enrolled in Cohort 5 (30 mg loading dose daily for 5 days followed by a maintenance dose of 30 mg twice a week).
DCC-3014 was generally well-tolerated, with no grade 3 or higher treatment-emergent adverse events (TEAEs) observed.
Two patients remained on study as of the November data analyses date. One patient discontinued in Cycle 4 due to relocation outside of the U.S.
Dose-escalation evaluation is ongoing to determine the recommended Phase 2 dose for advanced solid tumors and diffuse-type TGCT.
Results from the INVICTUS Pivotal Phase 3 Study of Ripretinib

An encore presentation of results from the INVICTUS pivotal Phase 3 study of ripretinib in advanced GIST will be featured during an oral presentation session. INVICTUS is a randomized (2:1), double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability, and efficacy of ripretinib compared to placebo in 129 patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. As previously reported, the study achieved the primary endpoint of improved progression free survival (PFS) compared to placebo in patients with fourth-line and fourth-line plus GIST, as determined by blinded independent central radiologic review using modified RECIST version 1.1.

Based on the positive INVICTUS data, the Company expects to submit an NDA to the U.S. Food and Drug Administration (FDA) for ripretinib for the treatment of patients with advanced GIST who have prior treatment with imatinib, sunitinib and regorafenib in the first quarter of 2020.

Presentation Details

Poster Presentation:

Poster Title: Phase 1 study of DCC-3014 to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics, in patients with malignant solid and diffuse-type tenosynovial giant cell tumor
Author: Breelyn Wilky, M.D., Associate Professor, Department of Medicine, Division of Medical Oncology, University of Colorado Cancer Center, University of Colorado School of Medicine
Poster Viewing Reception Date and Time: Thursday, November 14, 2019, 5:30 – 6:30 PM JST
Location: 3rd Floor, Hilton Tokyo Hotel
Abstract Number: 3241734

Oral Presentation:

Poster Title: INVICTUS: A Phase 3, interventional, double-blind, placebo-controlled study to assess the safety and efficacy of ripretinib (DCC-2618) in patients with advanced gastrointestinal stromal tumors (GIST) who have received treatment with prior anticancer therapies (NCT03353753)
Session Title: GIST
Author: Jean-Yves Blay, M.D., General Director, Centre Léon Bérard and Université Claude Bernard Lyon 1, Lyon, France
Presentation Date and Time: Friday, November 15, 2019, 1:00- 1:12 PM JST
Location: Kiku Ballroom, Hilton Tokyo Hotel
Abstract Number: 3254072

A copy of each presentation is available at www.deciphera.com/science/presentation-publications/.

About DCC-3014

DCC-3014 is an investigational, orally administered, potent and highly selective inhibitor of CSF1R. DCC-3014 was designed using the Company’s proprietary switch control kinase inhibitor platform to selectively bind to the CSF1R switch pocket. DCC-3014 has greater than 100-fold selectivity for CSF1R over other closely related kinases and has an even greater selectivity for CSF1R over approximately 300 other human kinases. CSF1R controls the differentiation and function of macrophages including tumor-associated macrophages (TAMs) whose density within certain tumors including cancers of the breast, cervix, pancreas, bladder and brain, as well as tenosynovial giant cell tumors (TGCT), correlates with poor prognosis. Tumors induce TAMs to suppress a natural immune response mediated by cytotoxic T-cells, a type of lymphocyte that would otherwise eradicate the tumor; a process known as macrophage checkpoints. Through inhibition of CSF1R, DCC-3014 has in preclinical studies demonstrated potent macrophage checkpoint inhibition as both a single agent and in combination with PD1 inhibitors. DCC-3014 is currently being evaluated in a Phase 1 clinical study. For more information about the clinical trial design please visit www.clinicaltrials.gov (NCT03069469).

About Ripretinib

Ripretinib is an investigational tyrosine kinase switch control inhibitor that was engineered to broadly inhibit KIT and PDGFRα mutated kinases by using a unique dual mechanism of action that regulates the kinase switch pocket and activation loop. Ripretinib is currently in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, or GIST, systemic mastocytosis, or SM, and other cancers. Ripretinib inhibits initiating and secondary KIT mutations in exons 9, 11, 13, 14, 17, and 18, involved in GIST, as well as the primary D816V exon 17 mutation involved in SM. Ripretinib also inhibits primary PDGFRα mutations in exons 12, 14 and 18, including the exon 18 D842V mutation, involved in a subset of GIST. In June 2019, the U.S. FDA granted Fast Track Designation to ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib. In October 2019, FDA granted Breakthrough Therapy Designation (BTD) for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib. For more information about the Company’s clinical trials with ripretinib, please visit www.clinicaltrials.gov.

Deciphera Pharmaceuticals has an exclusive license agreement with Zai Lab (Shanghai) Co., Ltd. for the development and commercialization of ripretinib in Greater China (MainlandChina, Hong Kong, Macau and Taiwan). Deciphera Pharmaceuticals retains development and commercial rights for ripretinib in the rest of the world.

On November 13, 2019 Medigene AG (Medigene, FSE: MDG1), a clinical stage immuno-oncology company focusing on the development of T cell immunotherapies, reported on its business performance and financial results for the first nine months of 2019 and confirms the financial guidance (Press release, MediGene, NOV 13, 2019, View Source [SID1234551163]).

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The full version of the quarterly statement 9M-2019 can be downloaded here: View Source

Prof. Dolores Schendel, CEO/CSO of Medigene AG commented: "In the past nine months, we have continued to work intensively on the progress of our immunotherapies. Preparations are ongoing for our next clinical trial with the T cell receptor (TCR) immunotherapy MDG1021 in cancer patients suffering from a disease relapse after hematopoietic stem cell transplantation. This trial will start next year and will be conducted in cooperation with the Leiden University Medical Center.
Our first-in-human clinical phase I/II trial with MDG1011 in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS) and multiple myeloma (MM) continues to recruit patients. While recruitment has been below desired levels we have adapted the study protocol and successively expanded the study centers. We expect data from the first three dose cohorts to be available in Q4 2020. We plan to further expand our pipeline of potential TCR candidates and are continuously researching the innovation potential of our technologies. We aim to increase the number of possible targets for our TCRs and are developing innovative next-generation TCR therapies, especially for difficult conditions such as the immunosuppressive environments in solid tumors. After promising interim data for our dendritic cell (DC) vaccine, we expect the topline results to be reported at the beginning of next year. Our partnerships as well as our finances are on track and we look forward to the coming months."

Major events since the beginning of 2019
– Medigene enters a clinical trial agreement for its second TCR immunotherapy MDG1021 with Leiden University Medical Center. Phase I clinical trial with the HA-1-specific TCR therapy scheduled to start in 2020
– Medigene publishes interim analysis from ongoing Phase I/II clinical trial with DC vaccines in acute myeloid leukemia (AML) patients at the Congress of the European Hematology Association (EHA) (Free EHA Whitepaper)
– bluebird bio presents preclinical data of the first TCR candidate from the Medigene collaboration and announces that clinical development of the TCR candidate targeting the MAGE-A4 tumor antigen, which is expressed on a variety of solid tumor types, will start in 2020
– Medigene doses the first patient in Phase I/II clinical trial of Medigene’s first T cell immunotherapy MDG1011 to treat the blood cancers: AML, MDS, and MM, and opens additional clinical trial centers
– Medigene and Roivant/Cytovant enter into a strategic partnership for the research and discovery of cell therapies in Asia. Medigene receives upfront payment of USUSD10 m and reimbursement of future R&D expenditure, potential milestone payments and royalties
– Medigene licenses a co-stimulatory receptor to enhance TCR therapies for solid tumors
– Medigene presents the results from in vitro tests to assess the potential TCR-mediated off-target toxicity for neuronal cells at the annual meeting of the American Society of Gene & Cell Therapy (ASGCT) (Free ASGCT Whitepaper)
– Medigene presents preclinical data on the selective killing of tumor cells by PRAME TCR-transduced T cells at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) conference
– Medigene presents its new ‘inducible Medigene (iM)-TCR’ which enables controllable cytotoxicity of tumor-specific TCR-T cells to potentially tune safety and efficacy according to clinical needs at the CAR-TCR Summit 2019
– Medigene obtains two European patents for its DC vaccine platform and for a TCR building block library to develop neoantigen-specific TCRs
– Medigene sells the remaining rights and stocks of Veregen to Aresus Pharma and thereby completes its transformation into a pure-play immunotherapy company

Key figures in the first three quarters of 2019
– Revenue from the core business of immunotherapies increased by 32% to Eur 6.2 m (9M 2018: Eur 4.7 m)
– Research and development expenses increased as expected by 24% to Eur 16.5 m (9M 2018: Eur 13.3 m) due to more intense activities in the development and production activities for Medigene’s immunotherapy programs
– EBITDA loss increased as anticipated by 48% to Eur 18.6 m (9M 2018: Eur 12.6 m*) (without taking the non-core business Veregen effect into account: increase of EBITDA loss by 11% to Eur 13.9 m)
– Net loss for the period increased as expected by 52% to Eur 20.0 m (9M 2018: Eur 13.2 m*)
– Cash and cash equivalents and time deposits of Eur 60.5 m as at September 30, 2019 (December 31, 2018: Eur 71.4 m)
– Confirmation of financial guidance 2019

* IAS 8 correction – see note (3) to the consolidated financial statements

Outlook
Financial guidance 2019

Medigene confirms the financial guidance issued in the 6M-2019 financial statement.

– The company is expecting to generate total revenue of Eur 10 – 11 m in 2019.
– Due to progress in the development projects, Medigene is projecting research and development expenses of Eur 24 – 29 m and forecasts an EBITDA loss of Eur 23 – 28 m.
– This assessment does not include potential future milestone payments or cash flows from existing or future partnerships or transactions, as the timing and extent of such events depends to a large extent on external parties and therefore cannot be reliably predicted by Medigene.
– Based on its current planning, the Company has sufficient financial resources to fund business operations beyond the planning horizon of two years.

Immunotherapy Outlook

Current Phase I/II clinical trial with Medigene’s first TCR therapy MDG1011
Medigene commenced the Phase I/II clinical trial of its TCR-based T cell therapy MDG1011 and began treating patients in the first quarter of 2019. In 2019, the focus of the trial is the recruitment for the first dose cohorts to assess the safety and tolerability of the treatment with MDG1011.

Planned Phase I/II clinical trial with Medigene’s second TCR therapy MDG1021
Based on the Clinical Trial Agreement entered into with the Leiden University Medical Center in May 2019, Medigene plans to conduct a Phase I clinical trial with its TCR therapy MDG1021, targeting the HA-1 antigen. Medigene will assess the safety, feasibility and preliminary efficacy of MDG1021 in patients with relapsed or persistent hematologic malignancies after allogeneic hematological stem cell transplantation. The study is scheduled to start in 2020 as Medigene’s second company-sponsored clinical TCR-T trial. In preparation for the trial, Medigene first needs to establish the manufacturing process, develop the design of the trial and then obtain the official trial approval.

Development of additional TCR candidates
Now that a robust platform for the discovery and characterization of new TCR candidates has been fully established, building a solid pipeline of potential TCR development candidates is an important goal to secure future clinical programs for both internal and existing or future partners.
In 2019, in addition to the MDG1011 clinical trial, Medigene will therefore continue to work on characterizing new TCR candidates for future clinical trials under the responsibility and funding of Medigene and collecting preclinical data to prepare further clinical TCR trials.

Optimization of future TCR therapies for solid tumors
The new inducible Medigene (iM)-TCR approach as well as the chimeric co-stimulator receptor (the PD-1/4-1BB molecule) licensed from HMGU will be assessed in combination with Medigene’s tumor-specific TCR-Ts in preclinical models in order to optimize future TCR therapies for solid tumors.

TCR partnerships
Medigene continues its successful collaboration with bluebird bio and expects to make further progress on TCR candidate discovery. Within the framework of the partnership entered into with Roivant/Cytovant, Medigene will now, together with the collaboration partner, undertake the preparations to generate TCR constructs tailored specifically to Asian patient populations using its proprietary TCR discovery and isolation platform.

Dendritic cell vaccines (DCs)
Conclusion of the Phase I/II clinical trial at the end of 2019
Medigene will continue the current Phase I/II clinical trial for DC vaccines for the treatment of AML as planned and bring it to a conclusion at the end of 2019. Topline data will be reported in the beginning of 2020.

Conference call and webcast
A telephone conference in English will be held today at 2:00 pm CET (Munich/Frankfurt) / 8:00 am EST (New York) and transmitted live via webcast. Access and transmission of the synchronized presentation slides and a recording of the presentation will be available on the Medigene website at View Sourcewebcasts/