On March 28, 2019 Molecular Templates, Inc. (Nasdaq: MTEM, "Molecular" or "Molecular Templates"), a clinical-stage oncology company focused on the discovery and development of the company’s proprietary engineered toxin bodies (ETBs), which are differentiated, targeted, biologic therapeutics for cancer, reported financial results for the fourth quarter of 2018 (Press release, Molecular Templates, MAR 28, 2019, View Source [SID1234534730]). As of December 31, 2018, Molecular’s cash and investments totaled $98 million, and is expected to fund operations into the first half of 2021.

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"2018 was a year of important progress for Molecular Templates, marked by new clinical data for MT-3724, advancement of our preclinical pipeline, the CD38 partnership with Takeda, and a successful equity financing," said Eric Poma, Ph.D., Molecular Templates’ Chief Executive and Scientific Officer. "In 2019, we are excited to generate more clinical data from multiple Phase II studies with MT-3724, advance MT-5111 and TAK-169 into the clinic, and file an IND for MT-6035, our PD-L1 ETB with antigen seeding. We are also focused on business development activity to generate additional non-dilutive capital."

Company Highlights and Upcoming Milestones

Corporate

Molecular will present new data on its pipeline programs and technology platform in four posters at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2019, to be held March 29 – Apr 3, 2019 in Atlanta, Georgia. Presentations will feature data on 1) CD38-targeted ETB TAK-169, 2) CD20-targeted ETB MT-3724 in combination with chemotherapy or IMiDs, 3) PD-L1-targeted ETB for direct cell kill approach to PD-L1 expressing cancers, 4) Bispecific ETBs for targeted cancer treatment.
On February 19, 2019, Molecular strengthened its senior management team with the appointment of Roger J. Waltzman, M.D., as Chief Medical Officer. Dr. Waltzman is a board-certified medical oncologist with over 20 years of experience in the pharmaceutical and biotechnology industries, and in medical practice/academia. His career highlights include 9 years in senior drug development roles at Novartis Pharmaceuticals Corporation, including 6 years in positions of increasing responsibility at Novartis Oncology (2007–2013). He played a leading role in the development of highly successful Novartis branded oncology drugs, Glivec (imatinib) and Jakafi (ruxolitinib).
On November 9, 2018, Molecular presented a poster on its PD-L1 ETB with Antigen Seeding Technology (AST) program at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting in Washington D.C. The poster, titled "Identification and Functional Profiling of PD-L1 Targeted Engineered Toxin Bodies for Antigen Seeding Technology (AST) and Redirection of T cell Response to Tumors" summarized a series of preclinical experiments conducted by Molecular to create PD-L1 targeted ETBs that have antigen seeding properties and to analyze the mechanisms by which they can kill cancer cells.

TAK-169

Takeda and Molecular expect to file an IND and start a Phase I multiple myeloma trial in 2019 for TAK-169 (CD38 targeted ETB).

MT-3724

Molecular recently announced the initiation of a Phase II monotherapy study of MT-3724 in relapsed/refractory diffuse large B-cell lymphoma (DLBCL). This study has the potential to be pivotal. Molecular expects to provide an update on this study in 2H19, with final data expected in 2020.
Molecular is also conducting a Phase II combination study with MT-3724 and chemotherapy in earlier lines of DLBCL.
Molecular expects to initiate a second Phase II combination study with MT-3724 and Revlimid in earlier lines of DLBCL in 2Q19.
Molecular expects to report an update on both MT-3724 combination studies with MT-3724 in 2H19.

Research

Molecular expects to initiate a Phase I study in cancer patients for MT-5111, its ETB targeting HER2, in 2Q19.
Molecular expects to report an update on this study in 2H19.
Molecular expects to file an IND application for MT-6035, its ETB targeting PD-L1 (with antigen seeding), in 2H19.
Several other ETB candidates are in preclinical development, targeting both solid and hematological cancers.

Takeda Multi-Target Collaboration

Takeda and Molecular are conducting lead optimization for ETBs against two undisclosed targets selected by Takeda under the collaboration. Should Takeda exercise its option to license ETBs for both targets, Molecular would receive $25 million and would be eligible to receive up to $547 million in milestone payments and tiered royalties on sales.
Financial Results

The net loss attributable to common shareholders for the fourth quarter of 2018 was $6.6 million, or $0.18 per basic and diluted share. This compares with a net loss attributable to common shareholders of $6.9 million, or $0.26 per basic and diluted share, for the same period in 2017.

Revenues for the fourth quarter of 2018 were $4.7 million, compared to $0.8 million for the same period in 2017. Revenues for the fourth quarter of 2018 were comprised of revenues from collaborative research and development agreements with Takeda, and grant revenue from CPRIT. Total research and development expenses for the fourth quarter of 2018 were $7.6 million, compared with $4.7 million for the same period in 2017. Total general and administrative expenses for the fourth quarter of 2018 were $3.9 million, compared with $3.5 million for the same period in 2017.

The net loss attributable to common shareholders for the year ended December 31, 2018 was $30.3 million, or $1.02 per basic and diluted share. This compares with a net loss attributable to common shareholders of $24.1 million, or $2.11 per basic and diluted share, for 2017.

Revenues for the year ended December 31, 2018 were $13.3 million, compared to $3.4 million for 2017. These revenues were mainly comprised of revenues from collaborative research and development agreements with Takeda, and grant revenue from CPRIT. Total research and development expenses for the year ended December 31, 2018 were $30.2 million, compared with $9.5 million for 2017. Total general and administrative expenses for the year ended December 31, 2018 were $14.1 million, compared with $11.8 million for 2017.

On March 28, 2019 Celyad (Euronext Brussels and Paris, and NASDAQ: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell product candidates, reported full year 2018 consolidated financial results prepared in accordance with IFRS (Press release, Celyad, MAR 28, 2019, View Source [SID1234534759]).

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Christian Homsy, CEO of Celyad: "In 2018, we identified several significant opportunities to drive long-term growth by focusing our clinical pipeline on the development of CAR-T cell product candidates. This includes the ongoing program for our lead product candidate CYAD-01 as well as our non-gene edited allogeneic candidate CYAD-101. Following encouraging preliminary data from the THINK trial evaluating CYAD-01 as a monotherapy for the treatment of relpased / refactory acute myeloid leukemia (r/r AML) patients, our clinical hematological program for CYAD-01 now includes multiple approaches for evaluating CYAD-01 including the THINK schedule optimization cohorts as well as our DEPLETHINK trial. We look forward to providing clinical updates from both the Phase 1 THINK and DEPLETHINK trials throughout 2019."

"In addition, we have advanced our shRNA platform to design novel preclinical CAR-T product candidates including our next-generation NKG2D-based CAR-T, CYAD-02, and our CYAD-200 series of non-gene edited allogeneic CAR-T candidates. We look forward to advancing multiple shRNA-based CAR-T product candidates towards the clinic in 2020."

Full Year 2018 and Recent Business Highlights

CYAD-01 – Autologous NKG2D-based CAR-T
Hematologic malignancies (r/rAML/MDS)

THINK Phase 1 trial, evaluating CYAD-01 without preconditioning chemotherapy, showed 40% (four out of ten) of patients with AML/MDS achieved a complete response.

Further development to assess a more frequent dosing schedule of CYAD-01 without preconditioning chemotherapy for the treatment of r/r AML is ongoing.

Cohort 1 of the DEPLETHINK Phase 1 trial, which is anopen-label, dose-escalation trial with a single injection of CYAD-01 following standard CyFlu preconditioning, demonstrated that CYAD-01 is well-tolerated, with no dose-limiting toxicity or treatment-related grade 3 or above adverse events (AEs) observed in patients with r/r AML.

Solid tumors (mCRC):

The concurrent treatment of CYAD-01 with FOLFOX chemotherapy in the first cohort of the trial was well tolerated, with no occurrence of serious AEs (SAEs) nor increase in the rate of treatment-related AEs. In addition, initial data from the THINK CyFlu cohort (single injection of CYAD-01 following treatment with CyFlu) showed that treatment is well tolerated with no occurrence of SAEs nor an increase in the treatment-related AEs rate. In addition, preliminary translational data suggest an improvement in the cell expansion of CYAD-01 induced by the CyFlu preconditioning.

CYAD-101 – Allogeneic NKG2D-based CAR-T
In 2018 the Company initiated the open-label, dose escalation alloSHRINK trial evaluating the non-gene edited allogeneic CAR-T therapy, CYAD-101, administered concurrently with FOLFOX chemotherapy in the treatment of patients with unresectable metastatic colorectal cancer (mCRC).

Novel, next-generation, shRNA platform
In March 2019, Celyad held a Research & Development Day in New York highlighting its pipeline of preclinical CAR-T product candidates candidates for the treatment of hematological malignancies and solid tumors, based on its short hairpin RNA (shRNA) platform

Autologous settings: CYAD-02 is a next-generation autologous NKG2D-based CAR-T candidate incorporating shRNA technology to target NKG2D ligands MICA/MICB. Preclinical AML models for CYAD-02 show an encouraging increase in in vitro proliferation and in vivo persistence and anti-tumor activity leading the company to plan to submit an Investigational New Drug (IND) application for CYAD-02 in the first half 2020.

Allogeneic settings: In vivo data demonstrate that shRNA targeting of CD3ζ by shRNA protects against graft-versus-host disease (GvHD) to a level equivalent to CRISPR-Cas9 based knock-out , as well as a significant increase in persistence of allogeneic T cells using shRNA targeting when compared to CRISPR-Cas9 gene-editing technologies.

This encouraged the company to develop three disruptive first-in-class non-gene-edited allogeneic CAR-T candidates from the CYAD-200 series leveraging the shRNA SMARTvector platform:

CYAD-211: B-cell maturation antigen (BCMA) targeting CAR-T therapy for the treatment of multiple myeloma, which is expected to enter the clinic by mid-2020
CYAD-221: CD19 targeting CAR-T therapy for the treatment of B-cell malignancies, which is expected to enter the clinic by late 2020
CYAD-231: Dual specific CAR-T targeting NKG2D and an undisclosed membrane protein, which is expected to enter the clinic by early 2021

Expected milestones for 2019

Additional data from the Phase 1 dose-escalation THINK trial for CYAD-01 in r/r AML or MDS patients, including initial data from the schedule optimization portion of the trial;
Enrollment completion and initial data from the Phase 1 dose-escalation DEPLETHINK trial evaluating CYAD-01 with preconditioning chemotherapy in r/r AML or MDS patients;
Acceleration of the development strategy and refinement of the regulatory pathway plan for CYAD-01 for the treatment of r/r AML or MDS patients, including the initiation of a potential Phase 2 clinical trial;
Advancement towards an IND application with the preclinical development of next-generation NKG2D-based CAR-T, CYAD-02 ; and
Further pursue the development of the proprietary non-gene edited allogeneic shRNA platform and progress towards IND applications for the CYAD-200 series of shRNA-based CAR-T candidates.

The Company’s license and collaboration agreements have generated a revenue of €3.1 million in 2018. This includes €2.4 million from the exclusive license agreement signed with Mesoblast Ltd. focused on the development and commercialization of Celyad’s intellectual property rights related to C-CathEZ, a proprietary intra-myocardial injection catheter, as well as €0.7 million from the non-clinical supply agreement with ONO Pharmaceutical Co., Ltd. with respect to the product candidate development of CYAD-101 for their licensed territories.

Research & Development expenses totaled €23.6 million and €22.9 million for 2018 and 2017, respectively. The increase in 2018 is mainly driven by the key clinical studies on CYAD-01 and CYAD-101.

General and Administrative expenses increased by €1.1 million, primarily driven by a non-cash expenses associated with the vesting of warrants.

The Company’s other expenses amount to €8.4 million and include non-cash expenses of €6.6 million relating to liability reassessment required by International Financial Reporting Standards (IFRS) related to the advancement in the Company’s NKG2D-based CAR-T candidates. Overall, non-cash expenses for 2018 totaled €10.2 million.

Therefore, Company’s operating loss of recurring operations (REBIT) increased to €38.2 million compared to €26.6 million for the year 2017. Net operational cash burn, which excludes non-cash effects, was €27.2 million in 2018 compared to €31.2 million in 2017.

Loss for the year 2018 amounts to €37.4 million versus a net loss of €56.4 million for 2017.

Cash, cash equivalents and short-term investments totaled €49.7 million as of December 31, 2018 compared to €33.9 million on December 31, 2017. The Company confirms its previous guidance that existing cash, cash equivalents and short-term investments should be sufficient to fund operating expenses and capital expenditure requirements, based on the current scope of activities, until mid-2020.

Annual Report 2018

The Annual Report for the year ended December 31, 2018 is published today, March 28, 2019, on the website of the Company. The statutory auditor, BDO Réviseurs d’Entreprises SCRL, has confirmed that the audit, which is substantially complete, has not to date revealed any material misstatement in the draft consolidated financial statements, and that the accounting data reported in the press release are consistent, in all material respects, with the draft consolidated financial statements from which it has been derived. On March 28, 2019, date of the release of the Annual Report, Celyad published a press release relating to the appointment of Mr. Filippo Petti as Chief Executive Officer of the Company effective on April 1, 2019. As a consequence of this publication, Celyad decided to issue a supplement to the Annual Report in order to keep the Annual Report up to the date of the convening notice to the 2019 annual shareholders’ meeting. This supplement will be published on the website of the Company within the next days.

Conference Call Details

A conference call will be held on Friday, 29 March 2019, at 1 p.m. CET / 8 a.m. EDT to review the financial and operating results for full year 2018. Please dial-in five to ten minutes prior to the call start time using the number and conference ID below: Standard International Dial-In Number: +44 (0) 2071 928000; Conference ID: 8745558

On March 28, 2019 Heat Biologics, Inc. (NASDAQ: HTBX), a biopharmaceutical company developing therapies designed to activate a patient’s immune system against cancer, reported financial and clinical updates for the fourth quarter and year ended December 31, 2018 (Press release, Heat Biologics, MAR 28, 2019, View Source [SID1234534693]).

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Jeff Wolf, Heat’s CEO, commented, "We are making excellent progress advancing HS-110 and recently reported interim Phase 2 non-small cell lung cancer (NSCLC) data on HS-110 plus nivolumab at the ASCO (Free ASCO Whitepaper)-SITC Clinical Immuno-Oncology Symposium. Importantly, we observed a survival benefit in patients with low CD8+ "cold" tumors at baseline compared to high CD8+ patients. This Cohort B data was especially encouraging, as all of the enrolled patients had previously experienced disease progression while receiving an immune checkpoint inhibitor. Preliminary data suggest the addition of HS-110 to Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, Opdivo (nivolumab), may restore responsiveness to treatment after tumor progression on prior checkpoint inhibitor therapy. We believe we are the first company to present clinical data in advanced NSCLC with patients whose prior checkpoint inhibitor treatment has failed. The results have generated significant interest within the industry and oncology community."

"We also expanded our Phase 2 trial to dose patients with HS-110 in combination with Merck’s anti-PD1 checkpoint inhibitor, KEYTRUDA (pembrolizumab) with or without ALIMTA (pemetrexed), in patients receiving front-line maintenance therapy for advanced NSCLC."

"We look forward to filing our Phase 1 Investigational New Drug (IND) for our next-generation therapy (HS-130) in the first half of 2019. HS-130 in combination with HS-110 combines T-cell activation and co-stimulation, potentially providing superior immune activation at reduced treatment costs. Further, we also plan to submit an IND for a CPRIT-funded 70 patient Phase 1 clinical program of PTX-35 in the first half of 2019. PTX-35 is our novel co-stimulatory antibody designed to harness the body’s natural antigen-specific T cell immune activation mechanisms. We remain encouraged by the preliminary pre-clinical efficacy and safety data, which show a lack of adverse effects across a wide range of doses."

"We ended 2018 with approximately $28 million of cash, cash equivalents and short-term investments. We also are on track to receive an additional $6.9 million in Cancer Prevention Research Institute of Texas (CPRIT) grant funds for PTX-35 in the coming months. As a result, we believe we are well funded beyond completion of our Phase 2 HS-110 trial. As previously disclosed, we have been efficient in our use of funds, which has allowed us to operate under budget, further extending our runway on primarily clinical development programs."

Full Year 2018 Financial Results

Recognized $5.8 million of grant revenue for qualified expenditures under the CPRIT grant.

Research and development expenses were $16.2 million for the year ended December 31, 2018 compared to $8.3 million for the year ended December 31, 2017. The increase was primarily due to the increase enrollment in the Phase 2 portion of our multi-arm NSCLC clinical trial as well as the PTX expense as we continue pre-clinical development of the PTX-35 program.

General and administrative expenses were $7.0 million for the year ended December 31, 2018 compared to $6.4 million for the year ended December 31, 2017.

Net loss attributable to Heat Biologics was $15.7 million, or ($0.90) per basic and diluted share for the year ended December 31, 2018 compared to a net loss of $11.8 million, or ($3.08) per basic and diluted share for the year ended December 31, 2017.

As of December 31, 2018, the Company had approximately $28 million in cash, cash equivalents and short term investments.

On March 28, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reportd that it will host a conference call and webcast discussion regarding the positive topline results from its pivotal clinical trial of enfortumab vedotin in locally advanced or metastatic urothelial cancer, which were announced in a press release earlier today (Press release, Seattle Genetics, MAR 28, 2019, http://investor.seattlegenetics.com/news-releases/news-release-details/seattle-genetics-host-conference-call-positive-topline-results [SID1234534713]). Access to the event can be obtained as follows:

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LIVE access on Thursday, March 28, 2019

6:00 a.m. Pacific Time (PT) / 9:00 a.m. Eastern Time (ET)

Telephone 866-288-0540 (domestic) or +1 786-460-7199 (international); conference ID 3807860
Webcast available at www.seattlegenetics.com in the Investors section
REPLAY access

Telephone replay will be available until 5:00 p.m. PT on Monday, April 1, 2019 by calling 888-203-1112 (domestic) or +1 719-457-0820 (international); conference ID 3807860
Webcast replay will be available on the Seattle Genetics website at www.seattlegenetics.com in the Investors section

On March 28, 2019 Molecular Templates, Inc., (Nasdaq: MTEM) a clinical stage biopharmaceutical company focused on the discovery and development of Engineered Toxin Bodies (ETBs), a new class of targeted biologic therapies that possess unique mechanisms of action in oncology, reported the initiation of a single-agent Phase II study of MT-3724, a CD20-targeted ETB, in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients (Press release, Molecular Templates, MAR 28, 2019, View Source [SID1234534732]). This multicenter study will enroll up to 100 patients, in a staged manner, who have received at least two standard of care treatment regimens for DLBCL. As a monotherapy study in heavily pretreated patients, this study has the potential to be pivotal.

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"We have been highly encouraged by the responses observed in the Phase I/Ib study of MT-3724 in heavily pretreated DLBCL patients," said Eric Poma, Ph.D., CEO and CSO of Molecular Templates. "This Phase II study largely replicates the Phase Ib expansion cohort, but with more clinical sites for enrollment, an independent data safety monitoring board, and independent central review for efficacy. Given the high level of unmet need in advanced DLBCL, we hope that this study will confirm that MT-3724 provides a meaningful benefit for this difficult to treat patient population."

The Phase II study will initially enroll patients at sites in the United States, Canada and Europe. MT-3724 will be given as 50 mcg/kg intravenous (IV) infusions, with a maximal per dose limit of 6,000 mcg. The primary outcome measure is tumor response, while secondary objectives include safety and other efficacy measures. The Phase II dose of 50 mcg/kg was selected based on safety data, tumor responses observed at dose levels as low as 5 and 20 mcg/kg, and pharmacodynamic effects of CD20+ B-cell clearance observed at various doses in the Phase I/Ib study. The Phase II study will exclude patients with high levels of serum rituximab, given CD20 binding competition of rituximab with MT-3724.