Phase 1
Phase 2
Phase 3
Application
Therapeutic
area
Cardiovascular-
Metabolics
Oncology
Others

Edoxaban (JP)
(DU-176b / AF / FXa inhibitor)

Prasugrel (JP)
(CS-747 / Ischemic stroke / Anti-
platelet agent)

Esaxerenone (JP)
(CS-3150 / Hypertension /
MR antagonist)

Edoxaban (ASCA etc.)
(DU-176b / AF / FXa inhibitor)

Edoxaban (ASCA etc.)
(DU-176b / VTE / FXa inhibitor)

Denosumab (JP)
(AMG 162 / Breast cancer adjuvant /
Anti-RANKL antibody)

Nimotuzumab (JP)
(DE-766 / Gastric cancer / Anti-EGFR
antibody)

Vemurafenib (US/EU)
(PLX4032 / Melanoma Adjuvant / BRAF
inhibitor)

Quizartinib (US/EU/Asia)
(AC220 / AML-2
nd
/ FLT3-ITD inhibitor)

Quizartinib (US/EU/Asia)
(AC220 / AML-1
st
/ FLT3-ITD inhibitor)

Pexidartinib (US/EU)
(PLX3397 / TGCT / CSF-1R/KIT/FLT3-ITD
inhibitor)

Laninamivir (US/EU)
(CS-8958 / Anti-influenza /
out-licensing with Biota)

Mirogabalin (US/EU)
(DS-5565 / Fibromyalgia /
α
2
δ
ligand)

Mirogabalin (JP/Asia)
(DS-5565 / DPNP/
α
2
δ
ligand)

Mirogabalin (JP/Asia)
(DS-5565 / PHN /
α
2
δ
ligand)

CHS-0214 (JP)
(Etanercept BS / Rheumatoid
arthritis / TNF
α
inhibitor)

VN-0105 (JP)
(DPT-IPV / Hib vaccine)

Laninamivir (JP)
(CS-8958 / Anti-influenza / nebulizer)

Esaxerenone (JP)
(CS-3150 / DM nephropathy / MR
antagonist)

Patritumab (EU)
(U3-1287 / Anti-HER3 antibody)

Pexidartinib (US)
(PLX3397 / Glioblastoma /
CSF-1R/KIT/FLT3-ITD
inhibitor)

DS-1647 (JP)
(Glioblastoma / G47
Δ
virus)

Quizartinib (JP)
(AC220 / AML-2
nd
/ FLT3-ITD
inhibitor)

DS-1040
(Acute ischemic stroke / TAFIa inhibitor)

DS-2330
(Hyperphosphatemia)

DS-9231/TS23
(Thrombosis /
α
2-PI inactivating antibody)

DS-3032 (US/JP)
(MDM2 inhibitor)

PLX7486 (US)
(FMS / TRK inhibitor)

PLX8394 (US)
(BRAF inhibitor)

DS-6051 (US/JP)
(NTRK/ROS1 inhibitor)

PLX9486 (US)
(KIT inhibitor)

DS-3201 (JP/
US
)
(EZH1/2 inhibitor)

PLX73086 (US)
(CSF-1R inhibitor)

PLX51107 (US)
(BRD4 inhibitor)

DS-1971
(Chronic pain)

DS-1501 (US)
(Osteoporosis / Anti-Siglec-15 antibody)

DS-7080 (US)
(AMD / Angiogenesis inhibitor)

DS-2969 (US)
(
Clostridium difficile
infection
/GyrB inhibitor)

DS-5141 (JP)
(DMD / ENA oligonucleotide)

VN-0102/JVC-001 (JP)
(MMR vaccine)

Hydromorphone (JP)
(DS-7113 / Cancer pain / Opioid
μ
–
receptor agonist)

CL-108 (US)
(Acute pain / Opioid
μ
-receptor
agonist)

Intradermal Seasonal
Influenza Vaccine (JP)
(VN-100 / prefilled i.d. vaccine for
seasonal flu)

VN-0107/MEDI3250 (JP)
(Nasal spray flu vaccine)

Denosumab (JP)
(AMG 162 / Rheumatoid arthritis /
Anti-RANKL antibody)
Major R&D Pipeline

DS-8273 (US)
(Anti-DR5 antibody)

DS-8201 (JP/US)
(anti-HER2 ADC
）

DS-1123 (JP)
(Anti-FGFR2 antibody)

U3-1402 (JP)
(Anti-HER3 ADC)

DS-1001 (JP)
（
IDH1m inhibitor
）
As of May 2017
Red: Major changes after the FY2016 Q3 financial announcement on Ja
nuary 31, 2017
12. Major R&D Pipeline (Innovative pharmaceuticals
）
◆
Oncology (Late-stage
pipeline products)
Generic Name/Project Code Number
(Brand Name)
Class
Target indication
Region Stage
Dosage
Form
Partner
Target FY for
approval/launch
Anti-RANKL antibody
Breast cancer adjuvant
JP
P3 Injection
Amgen
2020
BRAF inhibitor
Melanoma adjuvant
US/EU
P3
Oral
–
–
US/EU/Asia P3
2018
US/EU/Asia P3
2021-
JP
P2
2018-
Tenosynovial Giant Cell Tumor (TGCT)
US/EU
P3
2019
Solid tumors
Asia
P1
–
Glioblastoma
US
P2
–
c-KIT Melanoma
Asia
P1/2
–
Melanoma, Solid tumors
US
P1/2
Merck & Co., Inc.
–
Anti-EGFR antibody
Gastric cancer
JP
P3 Injection InnoClMAb Pte Ltd
2
020
Anti-HER3 antibody
Head & neck cancer
EU
P2 Injection
–
–
Oncolytic HSV-1
Glioblastoma
JP
P2 Injection
ActiVec Inc.
–
Underline: change after FY2016 Q3 Financial Announcement in Jan
uary 2017
Denosumab/AMG 162
Ranmark (JP)
Additional indication
The fully human monoclonal antibody to target RANK Ligand, an e
ssential mediator of osteoclast formation.
Vemurafenib/PLX4032
Zelboraf
Additional indication. Licensee Roche is conducting the
study. Submission in 2017 is planned.
The molecular-targe
ted agent to inhibit BRAF V600E mutation.
Nimotuzumab/DE-766
Patritumab/U3-1287
Pexidartinib/PLX3397
CSF-1R/KIT/FLT3-ITD inhibitor
Oral
–
Quizartinib/AC220
DS-1647(G47

)
Granted SAKIGAKE designation from MHLW
Investigator Initiated Study is on-going
The third generation oncolytic herpes simplex virus type 1(HSV-
1), genetically-engineered to restrict virus replication to tum
or cells. This oncolytic virus therapy is expected equal or be
tter safety and better efficacy profile compare to
existing oncolytic virus.
As of May 2017
The humanized monoclonal antibody to target Epidermal Growth Fa
ctor Receptor(EGFR). This antibody is expected to be a best in
class EGFR, safety against the skin toxicity and the efficacy c
omparable to the other antibodies.
The fully human monoclonal antibody to target HER3, one of the
Epidermal Growth Factor Receptor (EGFR) family of proteins. HER
3 is overexpressed in many tumors of epithelial origin and HER
2/HER3 dimers and EGFR/HER3
dimers are expected more potent to induce tumor cell proliferat
ion than homodimers of HER2 or EGFR.
Including pigmented villonodular synovitis
Including TGCT
Combination with pembrolizumab in collaboration with Merck
The molecular-targeted agent to inhibit CSF-1R, KIT and FLT3-IT
D. This agent is expected to reduce tumor cell proliferation an
d expansion of metastases.
Remarks
FLT3-ITD inhibitor
Acute myeloid leukemia
Oral
–
Relapsed and refractory AML patients
Newly diagnosed AML patients
Relapsed and refractory AML patients
Kinase inhibitor against a receptor-type tyrosine kinase, FLT3.
Therapeutic effect for patients with acute myeloid leukemia ha
rboring FLT3-ITD mutation is expected.

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On May 11, 2017 Astellas Pharma Inc. (TSE: 4503, President and CEO: Yoshihiko Hatanaka, "Astellas") reported the discontinuation of ASP8273 treatment arm in the the late-stage SOLAR trial evaluating the efficacy and safety of ASP8273 versus erlotinib/gefitinib for the 1st line treatment metastatic or advanced unresectable non-small cell lung cancer (NSCLC) harboring sensitizing epidermal growth factor receptor (EGFR) mutation (Press release, Astellas, MAY 11, 2017, View Source [SID1234519003]).

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Following a recommendation by the trial’s Independent Data Monitoring Committee (IDMC), Astellas is voluntarily closing study randomization and is informing investigators that ASP8273 treatment must be discontinued. Astellas is also planning to terminate future development programs for ASP8273 in NSCLC following its governance process.

"We are disappointed to be discontinuing the ASP8273 program and want to thank the patients and physicians involved in the program for their commitment to seeking new treatments for patients with non-small cell lung cancer," said Steven Benner, M.D., senior vice president and global therapeutic area head, oncology development, Astellas.

No new patients are being enrolled in ASP8273 trials and all patients currently receiving ASP8273 are encouraged to speak with their physician about their treatment.

On May 11, 2017 Heat Biologics, Inc. ("Heat") (Nasdaq: HTBX), a leader in the development of novel therapies designed to activate a patient’s immune system against cancer, reported a business and clinical update for the first quarter ended March 31, 2017 (Press release, Heat Biologics, MAY 11, 2017, View Source [SID1234519012]).

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During the first quarter, Heat announced a number of major developments. First, it met the safety and efficacy endpoints in its Phase 1b lung cancer trial evaluating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo), enabling it to progress to Phase 2 clinical trials. Preliminary data suggests Heat’s therapeutic vaccine has the potential to significantly expand the percentage of patients responding to checkpoint inhibitors by increasing T cell activity within the tumor, thereby converting "cold’’ tumors into "hot" tumors.

"We are encouraged by these results, showing signs of synergistic efficacy with nivolumab," said Jeff Wolf, Heat’s founder and CEO. "Patients with increased levels of tumor infiltrating lymphocytes (TIL) at 10 weeks saw a durable benefit, with 75% (6 out of 8 of these patients) alive at the one-year follow-up point. Additionally, 60% of the patients (3 of the 5 patients) exhibiting low TIL experienced significant tumor reduction, which compares favorably to the 10% response rate of low TIL patients reported for existing data on nivolumab alone."

Researchers reported a strong correlation between T cell activation, tumor reductions and increased overall survival in the 12 of the 15 patients that were evaluable for ELISPOT analysis. Importantly, the timing of immune responses to HS-110 corresponded to the timing of observed clinical responses, and those responses appear to be sustained.

Mr. Wolf continued, "While checkpoint inhibitors have transformed the landscape in the fight against cancer, they are only effective as a monotherapy in a small minority of patients. Our approach has the potential to dramatically increase the response rate in the majority of patients who don’t respond to checkpoint therapy alone. As a result of the encouraging data in our checkpoint combination trials and the positive response from within the industry, we are now prioritizing combination therapies, with a particular emphasis on checkpoint inhibitors and T cell co-stimulators. As a result, we are discontinuing programs where we do not see an opportunity to immediately combine with checkpoints, such as our non-muscle invasive bladder cancer program, and will instead reallocate those resources to fund current and future checkpoint and T cell co-stimulator combination programs."

Heat recently completed the acquisition of Pelican Therapeutics, whose product candidates strengthen its portfolio in the emerging T cell activation space. Pelican’s approach has the potential to improve the durability of responses in combination with Heat’s vaccine platform, as well as others, by stimulating the production of "memory" CD8+ T cells, as supported by pre-clinical data. This acquisition also brings with it a $15.2 million grant awarded by the Cancer Prevention and Research Institute of Texas (CPRIT) to advance multiple products through preclinical development and at least one program through a 70-patient Phase 1 clinical trial.

"We believe our growing franchise in immuno-oncology and activating cytotoxic T cells places us in a unique position at the core of future combination therapies," Wolf said. "We plan to continue to remain at the forefront in the development of exciting new therapies to activate T cells as part of a broad-based combination approach against cancer."

Heat ended the quarter with over $11 million in cash, and $15 million in non-dilutive grant funding through Pelican.

Recent Developments & First Quarter 2017 Corporate Highlights

·
In April 2017, Heat acquired an 80% controlling interest in Pelican Therapeutics, Inc. As of the acquisition date, Pelican is structured as a subsidiary to Heat focused on developing agonists to TNFRSF25, a highly differentiated and potentially "best-in-class" T cell costimulatory receptor. Pelican was the recipient of a highly-competitive $15.2 million New Company Product Development Award from the Cancer Prevention and Research Institute of Texas (CPRIT), which will enable the Company to advance multiple products through preclinical development and at least one program through a 70-patient Phase 1 clinical trial.

·
In April 2017, Heat presented new preclinical data from its collaboration with OncoSec Medical Incorporated at the AACR (Free AACR Whitepaper) Annual Meeting. Results suggested that combining ComPACT DNA electroporation and cellular vaccination led to increased tumor antigen-specific CD8+ T cells, delayed tumor progression and improved overall survival in preclinical models. The data demonstrated possible synergistic benefits of vaccination plus intratumoral injection.

·
In March 2017, Heat reported positive interim results from its Phase 2 clinical trial evaluating HS-110 in combination with Bristol-Myers Squibb’s anti-PD-1 checkpoint inhibitor, nivolumab (Opdivo) for the treatment of non-small cell lung cancer (NSCLC). Fifteen patients had completed the HS-110/nivolumab combination to-date and 12 of these 15 patients were evaluable for ELISPOT analysis. ELISPOT results suggest that HS-110 plays an integral role in tumor reduction and may enhance efficacy of checkpoint inhibitors in lung cancer patients.

[htbx_ex99z1001.jpg]

·
In March 2017, Heat announced that Natasa Strbo, M.D., D.Sc., Research Assistant Professor of Microbiology and Immunology at the University of Miami Miller School of Medicine, received a three-year $981,901 grant from the Florida Department of Health 2016-17 Zika Research Grant Initiative to further develop and test gp96-based Zika vaccine. This vaccine is being developed under a collaboration between the University of Miami and Heat’s wholly-owned subsidiary, Zolovax, Inc., which has licensed the intellectual property from the University of Miami.

·
In March 2017, Heat announced that it had achieved the safety and efficacy endpoints for its Phase 1b trial evaluating HS-110 in combination with nivolumab for the treatment of NSCLC and that the trial met the expansion criteria to advance into a Phase 2. Five out of 15 patients treated with the HS-110/nivolumab combination had 20% or greater tumor reduction. Patients with increased levels of tumor infiltrating lymphocytes (TIL) at 10 weeks appeared to have a durable benefit, with six out of eight of these patients (75%) alive at the one-year follow-up point.

·
In January 2017, Heat announced the appointment of Jeff Hutchins, Ph.D., as its Chief Scientific Officer and Senior Vice President of Preclinical Development. Dr. Hutchins brings over 24 years of research and clinical development experience from both large pharmaceutical and biotechnology companies.

First Quarter 2017 Financial Highlights

·
Research and development expenses decreased to approximately $1.9 million in the first quarter of 2017 from $3.7 million in the first quarter of 2016, a decrease of $1.8 million. The decrease is attributable to reductions in clinical trial costs, professional and consulting fees, personnel-related expenses, travel and other costs.

·
General and administrative expenses increased to $1.5 million in the first quarter of 2017 from $1.0 million in the first quarter of 2016, an increase of $0.5 million. The increase is attributable to professional services and third-party expenses related to the acquisition of Pelican.

·
Net loss for the first quarter of 2017 was $3.2 million compared to a net loss of $4.7 million for the first quarter of 2016.

· Cash and cash equivalents totaled approximately $11.1 million at March 31, 2017 compared to $7.8 million at December 31, 2016. Through the acquisition of Pelican, the Company also has access to a $15.2 million grand from CPRIT, which will enable it to advance multiple products through preclinical development and at least one program through a 70-patient Phase 1 clinical trial.

Burzynski Research Institute has filed a 10-K – Annual report [Section 13 and 15(d), not S-K Item 405] with the U.S. Securities and Exchange Commission .

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On May 10, 2017 Stemline Therapeutics, Inc. (Nasdaq: STML), a clinical-stage biopharmaceutical company developing novel therapeutics for oncology indications of unmet medical need, reported financial results for the quarter ended March 31, 2017 (Press release, Stemline Therapeutics, MAY 10, 2017, View Source [SID1234519066]). The company also reviewed clinical and regulatory events from the past quarter, and outlined key upcoming milestones:

SL-401 In Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

· During the quarter, we announced completion of enrollment in the Stage 3 cohort of the Phase 2 trial. Stage 3 enrolled 13 patients, and statistical analysis will be conducted on evaluable first-line BPDCN patients.

· Depending on the data from the trial, we plan to use the results generated, along with other relevant data, to support the potential filing of a Biologics License Application (BLA) for approval in BPDCN. A possible BLA filing could begin in 4Q17 or 1Q18.

· To ensure ongoing patient access to SL-401, we are enrolling both first-line and relapsed/refractory BPDCN patients under the current protocol in a Stage 4 cohort.

· We plan to provide an update on Stage 1 and 2 patients mid-year at an upcoming hematology-focused medical conference and on Stage 3 patients in the second half of the year.

Additional Clinical Trials

· Clinical trials evaluating SL-401 are ongoing in additional indications including certain myeloproliferative neoplasms (MPN), acute myeloid leukemia (AML) in complete remission with minimal residual disease, and relapsed/refractory multiple myeloma, and we expect to provide updates on these studies later this year and into next year.

· SL-801 is being evaluated in a Phase 1 dose escalation trial of advanced solid tumor patients, and we recently opened the sixth dosing cohort. SL-701 has completed dosing in a Phase 2 trial in second-line glioblastoma. Updates from both of these studies are expected later this year and into next year.

First Quarter 2017 Financial Results Review

Stemline ended the first quarter of 2017 with $105.8 million in cash, cash equivalents and investments, as compared to $67.6 million as of December 31, 2016, which reflects a cash increase of $38.2 million for the quarter. The $38.2 million increase in cash represents the $48.2 million in net cash proceeds received from the company’s follow-on public offering during January 2017 offset by a $10.0 million cash burn for operating activities during the first quarter 2017. The company ended the first quarter of 2017 with 25.1 million shares outstanding.

For the first quarter of 2017, Stemline had a net loss of $14.6 million, or $0.67 per share, compared with a net loss of $9.0 million, or $0.51 per share, for the same period in 2016.

Research and development expenses were $9.6 million for the first quarter of 2017, which reflects an increase of $3.1 million, or 47%, compared with $6.5 million for the first quarter of 2016. The higher costs are primarily driven by an increase of $2.3 million in manufacturing development expenses to support our upcoming potential BLA filing for SL-401. The manufacturing development costs include process characterization and process development work relating to the manufacture of drug substance and drug product for SL-401. Additionally, we incurred an increase in costs due to higher compensation expense as a result of increased headcount. Partially offsetting these higher expenses was a decrease in clinical trial costs for SL-701 resulting from the study attaining full patient enrollment during 2016.

General and administrative expenses were $5.4 million for the first quarter of 2017, which reflects an increase of $2.5 million, or 87%, compared with $2.9 million for the first quarter of 2016. The increase in expense was attributable to higher legal and audit fees of $1.9 million as a result of the class action lawsuits filed against us arising from our January 2017 follow-on public offering. Additionally, the higher costs were driven by $0.5 million in commercial-related pre-launch expenses in support of preparing for a potential product launch of SL-401 in BPDCN if marketing approval from the FDA is received.

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