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21ST CENTURY THERAPEUTICS, INC.

Address

440 BURROUGHS ST STE 100
DETROIT, MI, 48202-3428
USA

UEI: YR4CUFNLGKL8

Number of Employees: 9

HUBZone Owned: Yes

Woman Owned: No

Socially and Economically Disadvantaged: No

SBIR/STTR Involvement

Year of first award: 2009

Phase I Awards

Phase II Awards

33.33%

Conversion Rate

$618,127

Phase I Dollars

$1,133,678

Phase II Dollars

$1,751,805

Total Awarded

Awards

Up to 10 of the most recent awards are being displayed. To view all of this company's awards, visit the Award Data search page.

Development of a novel small molecule, UTL-5g, to treat oxaliplatin-induced throm

Amount: $276,418 Topic: NCI

DESCRIPTION (provided by applicant): Although oxaliplatin is a third-generation platinum drug, it has become the most prescribed amongst all platinum drugs overtaking its predecessors, cisplatin and carboplatin. To date, oxaliplatin has become an integralpart of various chemotherapy protocols, especially in advanced colorectal cancer. For colorectal cancer, oxaliplatin has been used with folinic acid (leucovorin) and 5-flurouracil (5-FU); this combination, referred to as FOLFOX, is now a treatment standardfor colorectal cancer. Unfortunately, like many other anticancer drugs, oxaliplatin has several significant side effects, most notably, thrombocytopenia. The use FOLFOX is well established and widely used for colorectal cancer. However, thrombocytopenia has been noted in more than 70% of patients receiving FOLFOX. As of today, there is no FDA approved drug indicated specifically for treating oxaliplatin-induced thrombocytopenia. Therefore, it is of great importance to develop a new agent specifically for oxaliplatin-induced thrombocytopenia. The ultimate goal of this project is t develop a novel small-molecule TNF- modulator, UTL-5g, to be used in conjunction with oxaliplatin for the treatment of colon cancer to significantly reduce oxaliplatin-induced thrombocytopenia. In this SBIR phase I study, several preclinical studies will be conducted to achieve the following specific aims: Aim 1. To show that, in a dose dependent manner, UTL-5g increases number of platelets lowered by oxaliplatin in vivo (a) To determine the nadir of platelet count after oxaliplatin treatment at the MTD (i.e., how many days after oxaliplatin treatment will platelet level be the lowest?). (b) To define the relationship of dose/schedule of UTL-5g and blood platelet counts. (c) To blend the schedule and doses obtained from (a) and (b) to show the effectiveness of UTL-5g in ameliorating the platelet suppression induced by oxaliplatin. For all these studies, when applicable, we will conduct counts/analyses on platelets, WBC, bone marrowand CD41+ megakaryocytes. We will also monitor the injuries on liver and kidney by analyzing AST, ALT, BUN, and creatine. In addition, cytokines, including TNF- and IL-10 (both are significantly reduced by oxaliplatin) will be assayed. Aim 2. Based on aim1, to select a dose range and conduct a therapeutic assessment to show that UTL-5g does not affect the anticancer activity of oxaliplatin (using a human colorectal cell line, HCT-15). Once this SBIR Phase I study is successfully completed, we will have shown the feasibility that UTL-5g can be used in conjunction with oxaliplatin to relieve oxaliplatin-induced thrombocytopenia and UTL-5g is a promising adjuvant agent worthy of continued preclinical development. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The ultimate goal of this project is to develop a novel small-molecule TNF- modulator, UTL-5g, to be used in conjunction with oxaliplatin for the treatment of colon cancer to significantly reduc oxaliplatin-induced thrombocytopenia.

SBIR

Phase I

2013

HHS

NIH

Novel small-molecule TNF-a modulators as chemoprotective agents

Amount: $1,133,678 Topic: NCI

DESCRIPTION (provided by applicant): Cisplatin is a widely used cytotoxic agent with therapeutic activity against various tumors, but also with substantial side effects, including nephrotoxicity, hepatotoxicity and myelosuppression. Therefore, a chemoprotective agent which reduces the side effects of cisplatin without affecting its efficacy would have significant clinical benefit. Currently, amifostine is the only FDA approved chemoprotective drug for cisplatin therapy. Amifostine is a sulfur-containing agent that reduces side effects resulted from both chemotherapy (including cisplatin) and radiotherapy regimens. Unfortunately, there are significant limitations associated with amifostine including its potentially serious side effects and potential tumor-protective effect. An ideal chemoprotector should not interfere with cisplatin's therapeutic effect, and with little or no toxicity by itself. As such, in our recently completed SBIR Phase I study, we investigated a small-molecule modulator of tumor necrosisfactor alpha (TNF-a), UTL-5g, as a leading chemoprotective agent. Based on this SBIR Phase I study, UTL-5g has been shown to reduce levels of blood urea nitrogen (BUN), creatinine, aspartate transaminase (AST), and alanine transaminase (ALT) elevated by cisplatin, indicating the protection of kidney and liver by UTL-5g. Blood levels of TNF-a elevated by cisplatin were also lowered by UTL-5g in a dose- dependent manner. An exciting finding is that not only UTL-5g did not reduce the antitumor effect of cisplatin in vivo, pre-treatment of UTL-5g actually increased the therapeutic effect of cisplatin. In addition, UTL-5g has a very low acute toxicity. All these exciting results from the SBIR Phase I study indicate that continued preclinical development is warranted. The specific aims of this SBIR Phase II study are: [Aim 1] Compare the chemoprotective effects by both oral gavage and ip injection (which was used in Phase I) in animal studies and determine the optimal oral dose of UTL-5g. If the ADME study shows that UTL-5g may be a pro-drug, we will also use the same protocol to study the chemoprotective effect of the metabolite(s). [Aim 2] Use the optimal oral dose of UTL-5g (determined in Aim 1) and increasing doses of cisplatin dose to find whether the MTD of cisplatin in mice can be increased by UTL-5g. If the MTD of cisplatin does increase, conduct a therapeutic assessment of cisplatin at the new MTD with and without UTL-5g. [Aim 3] Use the optimal oral dosage from Aim 1 to conduct the ADME study. [Aim 4] Scaleup the synthesis of API and prepare up to 1 kg of UTL-5g. [Aim 5] Conduct the 28-day repeat- dose toxicity studies in two species under GLP condition, employing the oral dosage form of UTL-5g. [Aim 6] Develop an oral formulation of UTL-5g suitable for thefirst clinical trial; develop and validate an analytical method for the oral formulation; define the specification and conduct a stability study on the oral dosage form. [Aim 7] Prepare a draft protocol suitable for the first Phase I clinical trial. [Aim8] Compile a pre-IND package in the format according to FDA's guidance for Industry and be ready for a pre-IND meeting with the FDA. PUBLIC HEALTH RELEVANCE: This SBIR Phase II study is the continuation of the successful SBIR Phase I study to conduct the preclinical development of a small-molecule TNF-a modulator, UTL-5g, as a chemoprotective agent to prevent/reduce side effects induced by cisplatin without compromising its therapeutic effect.

SBIR

Phase II

2011

HHS

NIH

TAS::75 0849::TAS

Amount: $186,857 Topic: NCI

Radiotherapy can potentially inflict serious damage on healthy normal organs. For example, pneumonitis and fibrosis are two well-recognized adverse effects from lung cancer radiotherapy: Currently, amifostine (Ethyol) is the only approved radioprotector indicated to reduce xerostomia associated with radiotherapy of head-and-neck cancer; there is no data supporting the radioprotection by amifostine. Several clinical studies indicated that TNF-61537; biologics may be effective in treating radiation pneumonitis. However, biologics are inconvenient to administer, and have been reported to be associated with potentially serious side effects. In this proposal, a small-molecule TNF-61537; modulator, UTL-5g, will be investigated for its potential to treat lung injury induced by radiation. The specific aims are: (1) To examine whether tumor cell-killing by irradiation is reduced by UTL-5g in vitro; (2) To show that UTL-5g is effective in reducing lung injury induced by irradiation in a dose-dependent manner in vivo; (3)To show that UTL-5g does not affect tumor cell-killing induced by irradiation in vivo. Successful completion of this study will prove the feasibility of using UTL-5g for treating radiation-induced lung injury. The ultimate goal of this project is to workwith or license to a major pharmaceutical company and develop a significantly improved radioprotector for lung radiotherapy.

SBIR

Phase I

2011

HHS

NIH

Novel Small-molecule TNF-a Modulators as Chemoprotective Agents

Amount: $154,852

DESCRIPTION (provided by applicant): Cisplatin is a widely used cytotoxic agent with therapeutic activity against various tumors, but also with substantial side effects, including nephrotoxicity, hepatotoxicity and myelosuppression. Therefore, a chemoprotective agent which reduces the side effects of cisplatin without affecting it efficacy would have significant clinical benefit. Currently, amifostine is the only FDA approved chemoprotective drug for cisplatin therapy. Amifostine is a sulfur-containing agent that reduces side effects resulted from both chemotherapy (including cisplatin) and radiotherapy regimens. Unfortunately, there are significant limitations associated with amifostine including (1) both amifostine and its active metabolite have very short half-lives in vivo requiring amifostine to be administered by a 15 minute infusion 30 minutes before cisplatin injection, and (2) amifostine is associated with side-effects including nausea and vomiting, as well as transient hypotension. Therefore, amifostine is not an ideal chemoprotector. An ideal chemoprotector should be orally administratable, with a longer half-life as compared to amifostine, and with little or no toxicity by itself. As such, we are proposing to investigate several novel small-molecule modulators of tumor necrosis factor alpha (TNF?), specifically UTL-5b, -5d, and -5g, as improved chemoprotective agents. UTL-5g will be the leading candidate for this Phase I study due to its promising biological effects and extremely low acute toxicity while UTL-5b and -5d will be backup compounds. UTL-5g is the subject compound in our recently completed SBIR Phase I grant for liver radioprotection (# 1 R43 CA117033-01A1). As a result, we have obtained promising results which are supportive of this proposal. The specific aims of this Phase I study are: (1) to conduct an animal study to show the chemoprotective effect of UTL-5g for cisplatin-induced side effects; the dose of UTL-5g with maximal protection will also be determined, (2) to conduct an animal study to show that UTL-5g does not decrease cancer killing during cisplatin therapy, and (3) to conduct a pharmacokinetic study to determine the half life of UTL-5g, and any metabolite(s). Once this phase I study is completed, we will know (1) whether UTL-5g reduces nephrotoxicity, hepatotoxicity, and/or myelosuppression induced by cisplatin in mice, (2) the optimal dose of UTL-5g for chemoprotection against cisplatin treatment in mice, (3) whether UTL-5g compromises cisplatin's anti-tumor activity in mice, and (4) the half-life of UTL-5g in mice and any metabolite(s). PUBLIC HEALTH RELEVANCE: This phase I study will focus on the feasibility of using a small-molecule TNF- modulator, UTL-5g, as a chemoprotector to prevent/reduce side effects induced by cisplatin.

SBIR

Phase I

2009

HHS

NIH