News Article | May 22, 2017
HAWTHORNE, N.Y.--(BUSINESS WIRE)--Taro Pharmaceutical Industries Ltd. (NYSE:TARO) (“Taro” or the “Company”) today provided unaudited financial results for the quarter and fiscal year ended March 31, 2017. Mr. Abhay Gandhi, Taro’s Interim CEO said, “As is commonly known, and as we have stated for quite some time, the entire generic sector, including Taro, is facing a challenging period. We continue to see a difficult generic pricing environment, particularly in the U.S., driven by intensified competition among manufacturers, new entrants to the market, buying consortium pressures, and higher ANDA approval rate from the FDA.” Mr. Gandhi continued, “Based on our well-balanced portfolio, the continuing focus on R&D investment, our healthy pipeline, and the Company’s strong balance sheet, we believe we are well positioned in our target markets.” The Company recently received approvals from the U.S. Food and Drug Administration (“FDA”) for four Abbreviated New Drug Applications (“ANDAs”): Brompheniramine Maleate, Pseudoephedrine Hydrochloride and Dextromethorphan Hydrobromide Syrup 2 mg/5 mL, 30mg/5 mL, 10 mg/5 mL, Metronidazole Gel USP, 1%, Tazarotene Cream, 0.1% and Felbamate Tablets, 400 mg and 600 mg. The Company currently has a total of thirty-five ANDAs awaiting FDA approval, including 5 tentative approvals. On November 23, 2016, the Company announced that its’ Board of Directors approved a new $250 million share repurchase of ordinary shares. This authorization follows the successful completion of the previous $250 million share repurchase program on August 19, 2016; under which, the Company bought back 1,801,099 of its ordinary shares, of which, 1,733,760 shares were purchased subsequent to April 1, 2016. Under the November 2016 authorization, repurchases may be made from time to time at the Company’s discretion, based on ongoing assessments of the capital needs of the business, the market price of its stock, and general market conditions. No time period has been set for the repurchase program, and any such program may be suspended or discontinued at any time. The repurchase authorization enables the Company to purchase its ordinary shares from time to time through open market purchases, negotiated transactions or other means, including 10b5-1 trading plans in accordance with applicable securities laws or other restrictions. During the fourth quarter, the Company repurchased 207,503 shares at an average price of $103.99. During the year, the Company repurchased 2,252,725 shares between the two programs. On March 16, 2017, BELLUS Health Inc.(“BELLUS”) announced that it had entered into a share purchase agreement with Taro for the sale of BELLUS’ wholly-owned subsidiary Thallion Pharmaceuticals Inc. (“Thallion”), including all the rights to the drug candidate Shigamab™. Pursuant to the agreement, Taro is acquiring all issued and outstanding shares of Thallion for a potential total consideration of CAD $2.7 million. In addition, BELLUS will receive a portion of certain post-approval revenues related to the Shigamab™ program. Development and Commercialization license to sell and distribute Pliaglis® On April 25, 2017, Crescita Therapeutics Inc. (“Crescita”), announced it had entered into a development and commercialization license agreement with Taro, under which, Crescita has granted Taro an exclusive license to the rights to sell and distribute Pliaglis® in the U.S. market and for a second-generation enhanced version with patent pending. As previously announced, the Company will host an earnings call at 8:00 am EDT on Tuesday, May 23, 2017, where senior management will discuss the Company’s performance and answer questions from participants. This call will be accessible through an audio dial-in and a web-cast. Audio conference participants can dial-in on the numbers below: To participate in the audio call, please dial the numbers provided above five to ten minutes ahead of the scheduled start time. The operator will provide instructions on asking questions before the call. The transcript of the event will be available on the Company’s website at www.taro.com. An audio playback will be available for twenty four (24) days following the call. Taro Pharmaceutical Industries Ltd. is a multinational, science-based pharmaceutical company, dedicated to meeting the needs of its customers through the discovery, development, manufacturing and marketing of the highest quality healthcare products. For further information on Taro Pharmaceutical Industries Ltd., please visit the Company’s website at www.taro.com. The unaudited consolidated financial statements have been prepared on the same basis as the annual consolidated financial statements and, in the opinion of management, reflect all adjustments necessary to present fairly the financial condition and results of operations of the Company. The unaudited consolidated financial statements should be read in conjunction with the Company’s audited consolidated financial statements included in the Company’s Annual Report on Form 20-F, as filed with the SEC. Certain statements in this release are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements that do not describe historical facts or that refer or relate to events or circumstances the Company “estimates,” “believes,” or “expects” to happen or similar language, and statements with respect to the Company’s financial performance, availability of financial information, and estimates of financial results and information for fiscal year 2018. Although the Company believes the expectations reflected in such forward-looking statements to be based on reasonable assumptions, it can give no assurances that its expectations will be attained. Factors that could cause actual results to differ include general domestic and international economic conditions, industry and market conditions, changes in the Company's financial position, litigation brought by any party in any court in Israel, the United States, or any country in which Taro operates, regulatory and legislative actions in the countries in which Taro operates, and other risks detailed from time to time in the Company’s SEC reports, including its Annual Reports on Form 20-F. Forward-looking statements are applicable only as of the date on which they are made. The Company undertakes no obligations to update, change or revise any forward-looking statement, whether as a result of new information, additional or subsequent developments or otherwise.
Mason W.P.,University of Toronto |
Belanger K.,Hopital Notre Dame |
Nicholas G.,Ottawa Hospital Regional Cancer Center |
Vallieres I.,Hotel Dieu de Quebec |
And 5 more authors.
Journal of Neuro-Oncology | Year: 2012
This phase II trial was undertaken to evaluate the efficacy of TLN-4601 in patients with glioblastoma (GBM) at first progression. TLN-4601 inhibits the RasMAPK signaling pathway, and in animal models crosses the blood-brain barrier and accumulates in implanted gliomas, possibly by binding specifically to the peripheral benzodiazepine receptor. A maximum of 40 patients with recurrent GBM were to be enrolled in this study. TLN4601 was administered at a dose of 480 mg/m2/day by continuous intravenous (CIV) administration. Each 21-day cycle consisted of a 14-day CIV administration and a 7-day recovery period. Samples were obtained from all patients for pharmacokinetic evaluations (PK) and for Raf1 and pERK biomarker assessment using immunohistochemistry and flow cytometry. Following enrollment of 20 patients, this study was terminated due to a lack of efficacy. Of 17 evaluable patients, 14 had MR scans performed after two cycles of TLN-4601. Of these 14 patients, three had stable disease and 11 had disease progression. Only three patients had MR scans performed after four cycles and all had evidence of radiographic progression. Serum PKs confirmed that patients were exposed to TLN-4601 at targeted drug levels. TLN-4601 was generally well tolerated although two patients discontinued treatment due to adverse events. Biomarker analysis did not show consistent changes. TLN-4601 infused via CIV at 480 mg/m2/day for 14 of 21 days is well tolerated by patients with progressive GBM. However, this agent is ineffective in progressive GBM when administered as monotherapy in this schedule. © Springer Science+Business Media, LLC. 2011.
Bitzan M.,McGill University |
Schaefer F.,University of Heidelberg |
Reymond D.,Thallion Pharmaceuticals Inc.
Seminars in Thrombosis and Hemostasis | Year: 2010
Typical enteropathic HUS (eHUS) is triggered by Shiga toxin (Stx)-producing bacteria (STPB), predominantly Stx-producing Escherichia coli O157. The cell biological aspects of Stx have been well defined, but host factors potentially predisposing to the development or severity of HUS remain elusive. Treatment of eHUS includes supportive measures and invasive extracorporeal therapies. Thirty to 60% of children with eHUS require dialysis. Peritoneal and hemodialysis appear equally effective. Patient age, center experience, and equipment availability determine the choice of the modality; circulatory instability may require continuous renal replacement therapies. At present, no evidence indicates that plasma infusion or exchange therapies improve outcome of Stx-induced HUS. However, the traditional separation between diarrhea-positive (D +) and negative (D -) HUS, implying two entirely different pathological pathways, requires a fresh look: Atypical HUS may follow nonspecific diarrhea, and, conversely, STPB and fecal Stx may not be detected anymore at the time of the diagnosis of HUS. Recently, Stx has been found to directly interfere with the alternative complement pathway regulator factor H in vitro, whereas some patients with Stx-HUS demonstrate evidence of complement activation. Among newer treatments for eHUS, development of Stx-neutralizing monoclonal antibodies is the most advanced. This review concludes with a discussion of the rationale, mode of action, and status of presently available therapeutic antibodies against Stx2 and Stx1. Copyright © 2010 by Thieme Medical Publishers, Inc.
Melton-Celsa A.R.,Uniformed Services University of the Health Sciences |
Carvalho H.M.,Uniformed Services University of the Health Sciences |
Thuning-Roberson C.,Thallion Pharmaceuticals Inc. |
O'Brien A.D.,Uniformed Services University of the Health Sciences
Clinical and Vaccine Immunology | Year: 2015
In the United States, Shiga toxin (Stx)-producing Escherichia coli (STEC) is the most frequent infectious cause of hemorrhagic colitis. Hemolytic uremic syndrome (HUS) is a serious sequela that may develop after STEC infection that can lead to renal failure and death in up to 10% of cases. STEC can produce one or more types of Stx, Stx1 and/or Stx2, and Stx1 and Stx2 are responsible for HUS-mediated kidney damage. We previously generated two monoclonal antibodies (MAbs) that neutralize the toxicity of Stx1 or Stx2. In this study, we evaluated the protective efficacy of human/mouse chimeric versions of those monoclonal antibodies, named cαStx1 and cαStx2. Mice given an otherwise lethal dose of Stx1 were protected from death when injected with cαStx1 either 1 h before or 1 h after toxin injection. Additionally, streptomycin-treated mice fed the mouse-lethal STEC strain B2F1 that produces the Stx2 variant Stx2d were protected when given a dose of 0.1 mg of cαStx2/kg of body weight administered up to 72 h post-oral bacterial challenge. Since many STEC strains produce both Stx1 and Stx2 and since either toxin may lead to the HUS, we also assessed the protective efficacy of the combined MAbs. We found that both antibodies were required to protect mice from the presence of both Stx1 and Stx2. Pharmacokinetic studies indicated that cαStx1 and cαStx2 had serum half-lives (t1/2) of about 50 and 145 h, respectively. We propose that cαStx1 and cαStx2, both of which have been tested for safety in humans, could be used therapeutically for prevention or treatment early in the development of HUS. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Bertomeu T.,Thallion Pharmaceuticals Inc. |
Zvereff V.,Thallion Pharmaceuticals Inc. |
Ibrahim A.,Thallion Pharmaceuticals Inc. |
Zehntner S.P.,Biospective Inc. |
And 6 more authors.
Biochemical Pharmacology | Year: 2010
TLN-4601 is a farnesylated dibenzodiazepinone isolated from Micromonospora sp. with an antiproliferative effect on several human cancer cell lines. Although the mechanism of action of TLN-4601 is unknown, our earlier work indicated that TLN-4601 binds the PBR (peripheral benzodiazepine receptor; more recently known as the translocator protein or TSPO), an 18. kDa protein associated with the mitochondrial permeability transition (mPT) pore. While the exact function of the PBR remains a matter of debate, it has been implicated in heme and steroid synthesis, cellular growth and differentiation, oxygen consumption and apoptosis. Using the Jurkat immortalized T-lymphocyte cell line, documented to have negligible PBR expression, and Jurkat cells stably transfected with a human PBR cDNA, the present study demonstrates that TLN-4601 induces apoptosis independently of PBR expression. As PBRs are overexpressed in brain tumors compared to normal brain, we examined if TLN-4601 would preferentially accumulate in tumors using an intra-cerebral tumor model. Our results demonstrate the ability of TLN-4601 to effectively bind the PBR in vivo as determined by competitive binding assay and receptor occupancy. Analysis of TLN-4601 tissue and plasma indicated that TLN-4601 preferentially accumulates in the tumor. Indeed, drug levels were 200-fold higher in the tumor compared to the normal brain. TLN-4601 accumulation in the tumor (176μg/g) was also significant compared to liver (24.8μg/g; 7-fold) and plasma (16.2μg/mL; 11-fold). Taken together our data indicate that while PBR binding does not mediate cell growth inhibition and apoptosis, PBR binding may allow for the specific accumulation of TLN-4601 in PBR positive tumors. © 2010 Elsevier Inc.
Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc and Thallion Pharmaceuticals Inc. | Date: 2012-03-06
The invention features methods, compositions, and kits for treating a subject having a Shiga toxin associated disease with chimeric anti-Shiga Toxin 1 (cStx1) and anti-Shiga Toxin 2 (cStx2) antibodies.
Thallion Pharmaceuticals Inc. and Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc | Date: 2013-01-16
The invention features methods, compositions, and kits for treating a subject having a Shiga toxin associated disease with chimeric anti-Shiga Toxin (cStx1) and anti-Shiga Toxin 2 (cStx2) antibodies
Thallion Pharmaceuticals Inc. | Date: 2010-04-21
The present invention provides a scalable process for producing a concentrate containing a mass of a farnesylated dibenzodiazepinone by fermenting in an aqueous culture medium a strain of a microorganism that is capable of producing the farnesylated dibenzodiazepinone, upon completion of fermentation harvesting the fermentation broth and extracting the fermentation broth to provide an extract, and thereafter treating the extract to form the concentrate. The concentrate so produced may be utilized in downstream processes for producing pharmaceutical compounds. A strain of a Micromonospora species capable of producing a farnesylated dibenzodiazepinone at a high yield rate is provided, together with culture media for culturing microorganisms, and fermentation conditions for production of the farnesylated dibenzodiazepinone of the concentrate.
Boufaied N.,Thallion Pharmaceuticals Inc. |
Wioland M.-A.,Thallion Pharmaceuticals Inc. |
Falardeau P.,Thallion Pharmaceuticals Inc. |
Gourdeau H.,Thallion Pharmaceuticals Inc.
Anti-Cancer Drugs | Year: 2010
TLN-4601 is a structurally novel farnesylated dibenzodiazepinone discovered through DECIPHER, Thallion's proprietary drug discovery platform. The compound was shown to have a broad cytotoxic activity (low μmol/l) when tested in the NCI 60 tumor cell line panel and has shown in-vivo antitumor activity in several xenograft models. Related to its farnesylated moiety, the effect of TLN-4601 on Ras mitogen-activated protein kinase signaling was assessed. Downstream Ras signaling events, Raf-1, MEK, and ERK1/2 phosphorylation in MCF7 cells were evaluated by western blot analysis. TLN-4601 prevented epidermal growth factor-induced phosphorylation of Raf-1, MEK, and ERK1/2. This effect was time-dependent and dose-dependent with complete inhibition of protein phosphorylation within 4-6 h at 10 μmol/l. The inhibition of Ras signaling was not mediated by the inhibition of protein prenylation, documented by the lack of effect TLN-4601 on the prenylation of HDJ2 (specific substrate of farnesyltransferase), RAP1A (specific substrate of geranylgeranyl transferase-1), or Ras. As TLN-4601 did not inhibit EGFR, Raf-1, MEK or ERK1/2 kinase activities, the inhibitory effect of TLN-4601 on Ras signaling is not mediated by direct kinase inhibition. Using an Elk-1 trans-activation reporter assay, we found that TLN-4601 inhibits the MEK/ERK pathway at the level of Raf-1. Interestingly, TLN-4601 induces Raf-1 proteasomal-dependent degradation. These data indicate that TLN-4601 may inhibit the Ras-mitogen-activated protein kinase-signaling pathway by depleting the Raf-1 protein. © 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
PubMed | Thallion Pharmaceuticals Inc. and Uniformed Services University of the Health Sciences
Type: Journal Article | Journal: Clinical and vaccine immunology : CVI | Year: 2015
In the United States, Shiga toxin (Stx)-producing Escherichia coli (STEC) is the most frequent infectious cause of hemorrhagic colitis. Hemolytic uremic syndrome (HUS) is a serious sequela that may develop after STEC infection that can lead to renal failure and death in up to 10% of cases. STEC can produce one or more types of Stx, Stx1 and/or Stx2, and Stx1 and Stx2 are responsible for HUS-mediated kidney damage. We previously generated two monoclonal antibodies (MAbs) that neutralize the toxicity of Stx1 or Stx2. In this study, we evaluated the protective efficacy of human/mouse chimeric versions of those monoclonal antibodies, named cStx1 and cStx2. Mice given an otherwise lethal dose of Stx1 were protected from death when injected with cStx1 either 1 h before or 1 h after toxin injection. Additionally, streptomycin-treated mice fed the mouse-lethal STEC strain B2F1 that produces the Stx2 variant Stx2d were protected when given a dose of 0.1 mg of cStx2/kg of body weight administered up to 72 h post-oral bacterial challenge. Since many STEC strains produce both Stx1 and Stx2 and since either toxin may lead to the HUS, we also assessed the protective efficacy of the combined MAbs. We found that both antibodies were required to protect mice from the presence of both Stx1 and Stx2. Pharmacokinetic studies indicated that cStx1 and cStx2 had serum half-lives (t1/2) of about 50 and 145 h, respectively. We propose that cStx1 and cStx2, both of which have been tested for safety in humans, could be used therapeutically for prevention or treatment early in the development of HUS.