Oncotelic Therapeutics, Inc 8-K, filed May 12, 2020
Oncotelic Therapeutics, Inc. (OTLC)
About this 8-K
Oncotelic Therapeutics, Inc filed this 8-K on May 12, 2020, reporting on events of May 10, 2020.
Items reported
- Item 8.01: Other events
- Item 9.01: Financial statements and exhibits
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
Current Report
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported)
May 10, 2020
MATEON THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
| Delaware | 000-21990 | 13-3679168 | ||
(State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
29397 Agoura Road, Suite 107
Agoura Hills, CA 91301
(Address of principal executive offices and Zip Code)
Registrant’s telephone number, including area code
(650) 635-7000
Not applicable.
(Former name or former address, if changed since last report.)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
| [ ] | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
| [ ] | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
| [ ] | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
| [ ] | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
| Title of class | Trading Symbols | Name of each exchange on which registered | ||
| N/A |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company [ ]
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. [ ]
Item 8.01 Other Events.
On May 10, 2020, Dr. Vuong Trieu, CEO of Mateon Therapeutics, Inc. (the “Company”), wrote a response to Remdesivir in covid-19. BMJ 2020; 369 doi: https://doi.org/10.1136/bmj.m1610 (Published 22 April 2020): BMJ 2020;369:m1610. Therapeutic strategies for COVID-19: New Insights Into The Value Of Transforming Growth Factor Beta (TGFβ) Antagonists Such As Imatinib and other Kinase Inhibitors.
TGF-Beta as the target for COVID-19 therapies.
Dear Editor:
I am encouraged that there is an emerging recognition that TGF-β could be a valid target for the treatment of COVID-19. Alhelfawi M. et al [1] suggested that COVID-19 can be treated with TGF-β inhibition. Chen W. [2], also put forth inhibition of TGF-β as treatment of COVID-19.
Coronavirus entry into cells is followed by suppression of cellular replication and redirection of cellular machineries to the replication of the virus. Cell cycle arrest is also centrally mediated by up-regulation of TGF-β. SARS coronavirus upregulates TGF-β [3,4] via its nucleocapsid protein [5] and papain-like protease (PLpro) [6,7]. SARS coronavirus PLpro activates TGF-β1 transcription both in cell-based assay and in mouse model with direct pulmonary injection [8]. TGF-β overexpression in SARS patients lung samples also been demonstrated. Suppression of TGF-β expression by OT-101 suppressed SARS-CoV1 and SARS-CoV2 replication in the viral replication assays [9]. This means as viral load increases there will be a proportional increase in TGF-β which in turn drives the progression of COVID-19 disease. By targeting TGF-β, OT-101 shuts off the engine behind COVID-19 allowing patients to recover without going into respiratory crisis. In fact, the administration of a soluble type II TGF-β receptor, which sequesters free TGF-β during lung injury and protected wild-type mice from pulmonary edema induced by bleomycin or Escherichia coli endotoxin [10].
Furthermore, mice specifically lacking bronchial epithelial TGF-b1 (epTGFbKO) displayed marked protection from influenza-induced weight loss, airway inflammation, and pathology. Additionally, these mice exhibited a heighted antiviral state resulting in impaired viral replication in epTGFbKO mice [11]. Their publication succinctly described the impact of TGF-β suppression against viral infection and we would propose that TGF-beta inhibitor would result in very similar if not the same protective responses against COVID-19.
A TGF-beta inhibitor is expected to broadly impacted COVID-19 disease and we would encourage developers of TGF-beta to collaborate and build on these observations such that we can arrive at a cure for COVID-19- either as single agent or combination with Remdesivir.
Regards
Vuong Trieu PhD
CEO/Mateon/ Oncotelic
Refs:
1. Alhelfawi M. Potential approach for fighting against corona virus disease. ASRJETS. 2020;66:127-144.
2. Chen W. A potential treatment of COVID-19 with TGF-β blockade. International Journal of Biological Sciences. 2020;16(11):1954-1955. Doi: 10.7150/ ijbs.46891.
3. Huang KJ, Su IJ, Theron M, Wu YC, Lai SK, Liu CC, Lei HY. An interferon-gamma related cytokine storm in SARS patients. J. Med. Virol. 2005;75(2):185-194.
4. He L, Ding Y, Zhang Q, Che X, He Y, Shen H, Wang H, Li Z, Zhao L, Geng J, Deng Y, Yang L, Li J, Cai J, Qiu L, Wen K, Xu X, Jiang S. Expression of elevated levels of pro-inflammatory cytokines in SARS-CoV infected ACE2+ cells in SARS patients: relation to the acute lung injury and pathogenesis of SARS. J. Pathol. 2006;210(3):288-297.
5. Zhao X, Nicholls JM, Chen YG. Severe acute respiratory syndrome-associated coronavirus nucleocapsid protein interacts with Smad3 and modulates transforming growth factor-beta signalling. J. Biol. Chem. 2008;283(6):3272-3280.
6. Li SW, Yang TC, Wan L, Lin YJ, Tsai FJ, Lai CC, Lin CW. Correlation between TGF-β1 expression and proteomic profiling induced by severe acute respiratory syndrome coronavirus papain-like protease. Proteomics. 2012;12(21):3193-3205.
7. Wang CY, Lu CY, Li SW, Lai CC, Hua CH, Huang SH, Lin YJ, Hour MJ, Lin CW. SAR coronavirus papain-like protease up-regulates the collagen expression through non-Samd TGF-β1 signaling. Virus Research. 2017;235:58-66.
8. Li SW, Wang CY, Jou YJ, Yang TC, Huang SH, Wan L, Lin YJ, Lin CW. SARS coronavirus papain-like protease induces Egr-1-dependent up-regulation of TGF-β1 via ROS/p38 MAPK/STAT3 pathway. Scientific Reports. 2016;6:25754.
9. Uckun FM and Trieu VN. Medical-Scientific Rationale for a Randomized, Placebo-Controlled, Phase 2 Study of Trabedersen/OT-101 in COVID-19 Patients with Hypoxemic Respiratory Failure. Anna pul and Cri Car Med..2020; 3(1); 01-09.
10. Pittet JF, Griffiths MJ, Geiser T, Kaminski N, Dalton SL, Huang X, Brown LA, Gotwals PJ, Koteliansky VE, Matthay MA, Sheppard D. TGF-beta is a critical mediator of acute lung injury. J Clin Invest. 2001;107(12):1537–44.
11. Denney L, Branchett W, Gregory LG, Oliver RA, Lloyd CM. Epithelial-derived TGF-β1 acts as a pro-viral factor in the lung during influenza A infection. Mucosal Immunology. 2018;11(2):523-535.
This is building on our growing conviction that COVID-19 is a TGF-β driven disease (press release filed as Exhibit 99.1) and the IND filing of OT-101 for COVID-19 (press release filed as Exhibit 99.2).
Forward-Looking Statements
This document contains “forward-looking statements” that involve substantial risks and uncertainties for purposes of the safe harbor provided by the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this communication regarding strategy, future operations, future financial position, prospects, plans and objectives of management are forward-looking statements. In addition, when or if used in this communication, the words “will,” “may,” “would,” “approximate,” “expect,” “intend,” and similar expressions and their variants may identify forward-looking statements. Examples of forward-looking statements include, but are not limited to, statements relating to the anticipated timing or results of the Company’s planned phase 3 trial for the OT101 product candidate, the Company’s ability to successfully secure any U.S. FDA priority review voucher, or the Company’s ability to sell and U.S. FDA priority review voucher or the terms of any such potential sale. Actual results could differ materially from those contained in any forward-looking statement as a result of various factors that could cause actual events to differ from expectations, including the risk factors included in the Company’s most recent Annual Report on Form 10-K and other periodic reports filed with the Securities and Exchange Commission. Except as required by applicable law, the Company undertakes no obligation to revise or update any forward-looking statement, or to make any other forward-looking statements, whether as a result of new information, future events or otherwise.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
Exhibit No. |
Description |
Incorporation by reference | ||
| 99.1 | Press Release | Filed herewith | ||
| 99.2 | Press Release | Filed herewith |
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
| Mateon Therapeutics, Inc. | ||
| Date: May 12, 2020 | /s/ Vuong Trieu | |
| By: | Vuong Trieu | |
| Chief Executive Officer | ||
Exhibit 99.1
Mateon Provides Update on its R&D Effort Against COVID-19
AGOURA HILLS, Calif., April 30, 2020 (GLOBE NEWSWIRE) – Mateon Therapeutics Inc. (OTCQB:MATN) report several peer-reviewed publications derived from its R&D effort against COVID-19.
Published April 24th, is a special report in the biomedical journal Annals of Pulmonary and Critical Care Medicine regarding the medical-scientific rationale for its planned randomized, placebo-controlled, Phase 2 Study of OT-101 in COVID-19 patients with hypoxemic respiratory failure.
In this publication, we are proposing that COVID-19 is a TGF-β driven disease treatable with TGF-β inhibitor such as Mateon’s OT-101. As the virus replicates it releases TGF-β which drives viral replication, drives water accumulation in the lung, and drives neutrophil mediated inflammation ultimately resulting in death from acute respiratory distress syndrome (ARDS) and its complications.
“We are advancing quickly the clinical development of OT-101 against COVID-19. We would encourage other developers of TGF-β inhibitors to work together to develop cure against this TGF-β driven disease.” said Dr Vuong Trieu, CEO of Mateon Therapeutics.
Viral replication is dependent on expression of TGF-β and the progressive increase in TGF-β with increasing viral load with has been implicated as an important pro-inflammatory cytokine in the pathophysiology of acute lung injury and ARDS that contributes to both increased permeability and failed fluid reabsorption in lungs leading to persistent and severe pulmonary edema. TGF-β profoundly impacts alveolar ion and fluid transport by regulating the epithelial sodium channel (ENaC) activity and trafficking via a Tgfbr1-mediated unique signaling pathway. TGF-β has been identified as the exclusive master regulator of ENAC internalization by alveolar epithelial cells and its upregulation in ARDS causes an ENAC trafficking defect with marked reduction in the cell-surface abundance of ENaC on lung epithelial cells thereby rapidly and substantially impairing alveolar fluid reabsorption in ARDS patients and contributing to the persistence of their pulmonary edema. Mateon’s anti-TGF-β RNA therapeutic OT101 exhibited nanomolar in vitro potency against SARS-CoV-2 and is potentially targeting the root cause of COVID-19.
Reference: Uckun FM, Trieu V. Medical-Scientific Rationale for a Randomized, Placebo-Controlled, Phase 2 Study of Trabedersen/OT-101 in COVID-19 Patients with Hypoxemic Respiratory Failure. Annals of Pulmonary and Critical Care Medicine 2020; 3(1); 01-09.
Reference: On April 20, 2020, Mateon published a peer-reviewed research article: David N, Hwang L, Cynthia L, Vuong N Trieu. COVID-19 Epidemic: China and ex-China. Open Acc Biostat Bioinform. 3(1). OABB.000552. 2020. DOI: 10.31031/OABB.2020.03.000552.
This study was performed to understand the spread of COVID-19 epidemic outside of China. Given the higher mortality rate than China and the failure to control the epidemic at the same 100-1000 confirmed cases as China, the COVID-19 epidemic outside of China is expected to be possibly be as severe as that of Hubei- the epicenter of the COVID-19 epidemic. It is noteworthy that the mortality curves and recovered curves are more similar to Hubei for ex-China. Of particular concern is the slow rise in recovery rate- even in Korea. This simple analysis indicated that extensive testing to control the epidemic prior to 1000 confirmed cases and the rapid recovery rate are critical to controlling COVID-19. Therapeutic intervention is important for the rapid recovery.
Reference: On April 23, 2020, we published an updated publication. Vuong N Trieu, David Nam, Larn Hwang, Cynthia Lee. COVID-19 Epidemic: China and Ex-China 4-23-2020
Update. Ther Res Skin Dis 1(4)- 2020. TRSD. MS.ID.000116. DOI: 10.32474/ TRSD.2020.01.000116.
In this update we examined US, UK, Italy, Spain, Korea. Using % recovery we determined that recovery exhibited the following decreasing order Korea, Spain, Italy, US, and UK, suggesting that UK is still deep in the epidemic while Korea, Spain, and Italy have exited the epidemic and US is late stage of the epidemic.
About Mateon
Mateon was created by the recent merger with Oncotelic – a developer of TGF-beta RNA therapeutics- and PoinTR- a cluster computer vision empowered blockchain company creating an immuno-oncology company dedicated to the development of first in class RNA therapeutics as well as small molecule drugs against cancer. The founding team members of Oncotelic were responsible for the development of Celgene’s Abraxane as a chemotherapeutic agent for breast, lung, melanoma, and pancreatic cancer. Abraxane was approved in 2005 and has more than $1B in sales annually. The same team was also responsible for the development of Cynviloq, a next generation Abraxane, which was acquired by NantPharma for $1.3B. Mateon/Oncotelic is seeking to leverage its deep expertise in oncology drug development to improve treatment outcomes and survival of cancer patients with a special emphasis on pediatric cancer patients. For more information, please visit www.oncotelic.com and www.mateon.com.
About Mateon’s Lead Product Candidate, OT-101
During phase 2 clinical trials in pancreatic cancer, melanoma, and colorectal cancers (Study P001) and in high-grade gliomas (Study G004), meaningful clinical benefits were observed and OT-101 exhibited a favorable safety profile. These clinical benefits included long term survival and meaningful tumor reduction. Both partial and complete responses have been observed in the G004 Phase 2 clinical trial of OT-101 as a single agent in patients with aggressive brain tumors. The company’s self-immunization protocol (SIP©) is based on novel and proprietary sequential treatment of cancers with OT-101 (an antisense against TGF-β2) and chemotherapies. This sequential treatment strategy is aimed at achieving effective self-immunization against a patients’ own cancer, resulting in robust therapeutic immune response and consequently better control of the cancer and improved survival. Prolonged states of being cancer-free have been observed in some patients with the most aggressive forms of cancer, raising a renewed hope for a potential cure. The use of OT-101 lifts the suppression of the patient’s immune cells around the cancer tissue, providing the foundation for an effective initial priming, which is critical for a successful immune response. The subsequent chemotherapy results in the release of neoantigens that result in a robust boost of the immune response.
Mateon’s Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this communication regarding strategy, future operations, future financial position, prospects, plans and objectives of management are forward-looking statements. Words such as “may”, “expect”, “anticipate” “hope”, “vision”, “optimism”, “design”, “exciting”, “innovative”, “promising”, “will”, “conviction”, “estimate,” “intend,” “believe”, “quest for a cure of cancer”, “innovation-driven”, “paradigm-shift”, “high scientific merit”, “impact potential” and similar expressions are intended to identify forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about future plans, the progress, timing, clinical development, scope and success of future clinical trials, the reporting of clinical data for the company’s product candidates and the potential use of the company’s product candidates to treat various cancer indications. Each of these forward-looking statements involves risks and uncertainties and actual results may differ materially from these forward-looking statements. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, failure of collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes. These risks are not exhaustive, the company faces known and unknown risks, including the risk factors described in the company’s annual report on Form 10-K filed with the SEC on April 10, 2019 and in the company’s other periodic filings. Forward-looking statements are based on expectations and assumptions as of the date of this press release. Except as required by law, the company does not assume any obligation to update forward-looking statements contained herein to reflect any change in expectations, whether as a result of new information future events, or otherwise.
Contact Information:
For Mateon Therapeutics, Inc.:
Amit Shah
Email: ashah@oncotelic.com
Exhibit 99.2
Mateon Announces the Filing of an IND with US FDA to Evaluate its Antisense Drug Candidate OT-101 in COVID-19 patients
AGOURA HILLS, Calif., April 27, 2020 (GLOBE NEWSWIRE) -- Mateon Therapeutics Inc. (OTCQB:MATN) announced today it has submitted an Investigational New Drug (IND) application to the US Food and Drug Administration (FDA) to study its investigational drug, OT-101, for the treatment of COVID-19 pandemic.
The proposed randomized, double-blind, placebo-controlled Phase 2 study is intended to evaluate the safety and efficacy of OT-101 in adult patients hospitalized with COVID-19 and pneumonia in the US.
OT-101 is a potent inhibitor of SAR-CoV2 replication with efficacy and safety index on par or superior to Remdesivir- a Gilead’s drug. Unlike Remdesivir- OT-101 targets not only the virus replication but also the often-lethal clinical sequelae of COVID-19, including pneumonia and fibrosis. OT-101 is a proprietary, first-in-class, TGF-β antisense with broad efficacy against solid tumors including pancreatic cancer, glioblastoma, and melanoma across multiple phase 2 oncology trials.
“We are advancing quickly the clinical development of OT-101 as multimodal drug against COVID-19. It is imperative to look at a basket of drug candidates to insure finding the cure for COVID-19. Additionally, an effective treatment for COVID-19 is more likely a cocktail of drugs,” said Dr Vuong Trieu, CEO of Mateon Therapeutics. “We look forward to collaborating closely with leading clinical investigators and the FDA to validate the effectiveness of OT-101 in treating COVID-19 in a controlled clinical setting.”
About Mateon
Mateon was created by the recent merger with Oncotelic – a developer of TGF-beta RNA therapeutics- and PoinTR- a cluster computer vision empowered blockchain company creating an immuno-oncology company dedicated to the development of first in class RNA therapeutics as well as small molecule drugs against cancer. The founding team members of Oncotelic were responsible for the development of Celgene’s Abraxane as a chemotherapeutic agent for breast, lung, melanoma, and pancreatic cancer. Abraxane was approved in 2005 and has more than $1B in sales annually. The same team was also responsible for the development of Cynviloq, a next generation Abraxane, which was acquired by NantPharma for $1.3B. Mateon/Oncotelic is seeking to leverage its deep expertise in oncology drug development to improve treatment outcomes and survival of cancer patients with a special emphasis on pediatric cancer patients. For more information, please visit www.oncotelic.com and www.mateon.com.
About Mateon’s Lead Product Candidate, OT-101
During phase 2 clinical trials in pancreatic cancer, melanoma, and colorectal cancers (Study P001) and in high-grade gliomas (Study G004), meaningful clinical benefits were observed and OT-101 exhibited a favorable safety profile. These clinical benefits included long term survival and meaningful tumor reduction. Both partial and complete responses have been observed in the G004 Phase 2 clinical trial of OT-101 as a single agent in patients with aggressive brain tumors. The company’s self-immunization protocol (SIP©) is based on novel and proprietary sequential treatment of cancers with OT-101 (an antisense against TGF-β2) and chemotherapies. This sequential treatment strategy is aimed at achieving effective self-immunization against a patients’ own cancer, resulting in robust therapeutic immune response and consequently better control of the cancer and improved survival. Prolonged states of being cancer-free have been observed in some patients with the most aggressive forms of cancer, raising a renewed hope for a potential cure. The use of OT-101 lifts the suppression of the patient’s immune cells around the cancer tissue, providing the foundation for an effective initial priming, which is critical for a successful immune response. The subsequent chemotherapy results in the release of neoantigens that result in a robust boost of the immune response.
Mateon’s Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. All statements, other than statements of historical facts, included in this communication regarding strategy, future operations, future financial position, prospects, plans and objectives of management are forward-looking statements. Words such as “may”, “expect”, “anticipate” “hope”, “vision”, “optimism”, “design”, “exciting”, “innovative”, “promising”, “will”, “conviction”, “estimate,” “intend,” “believe”, “quest for a cure of cancer”, “innovation-driven”, “paradigm-shift”, “high scientific merit”, “impact potential” and similar expressions are intended to identify forward-looking statements. Forward-looking statements contained in this press release include, but are not limited to, statements about future plans, the progress, timing, clinical development, scope and success of future clinical trials, the reporting of clinical data for the company’s product candidates and the potential use of the company’s product candidates to treat various cancer indications. Each of these forward-looking statements involves risks and uncertainties and actual results may differ materially from these forward-looking statements. Many factors may cause differences between current expectations and actual results, including unexpected safety or efficacy data observed during preclinical or clinical studies, clinical trial site activation or enrollment rates that are lower than expected, changes in expected or existing competition, changes in the regulatory environment, failure of collaborators to support or advance collaborations or product candidates and unexpected litigation or other disputes. These risks are not exhaustive, the company faces known and unknown risks, including the risk factors described in the company’s annual report on Form 10-K filed with the SEC on April 10, 2019 and in the company’s other periodic filings. Forward-looking statements are based on expectations and assumptions as of the date of this press release. Except as required by law, the company does not assume any obligation to update forward-looking statements contained herein to reflect any change in expectations, whether as a result of new information future events, or otherwise.
Contact Information:
For Mateon Therapeutics, Inc.:
Amit Shah
Email: ashah@oncotelic.com