On December 28, 2018 Medtronic plc (NYSE:MDT), the global leader in medical technology, reported it will participate in the 37th Annual J.P. Morgan Healthcare Conference in San Francisco (Press release, Medtronic, DEC 28, 2018, View Source;p=RssLanding&cat=news&id=2381699 [SID1234532302]).

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Omar Ishrak, Medtronic chairman and chief executive officer, will make a formal presentation on the company beginning at 9:00 a.m. PST (11:00 a.m. CST) on Monday, January 7, 2019. Shortly following the presentation, Ishrak and Karen Parkhill, executive vice president and chief financial officer, will answer questions on the company.

A live audio webcast of the presentation and Q&A session will be available on January 7, 2019, by clicking on the Investor Events link at View Source An archive of the presentation and Q&A session will be available on the same webpage later in the day.

On December 28, 2018 Alnylam Pharmaceuticals, Inc. (Nasdaq: ALNY), the leading RNAi therapeutics company, reported that management will present a company overview at the 37th Annual J.P. Morgan Healthcare Conference onMonday, January 7, 2019 at 10:30 am PT (1:30 pm ET) at The Westin St. Francis in San Francisco (Press release, Alnylam, DEC 28, 2018, View Source;p=RssLanding&cat=news&id=2381687 [SID1234532303]). This presentation will include an update on unaudited fourth quarter 2018 global net product revenues for ONPATTRO (patisiran) as well as additional updates on the product’s commercial launch. In addition, the Company will webcast the Q&A breakout session immediately following its presentation at 11:00 am PT (2:00 pm ET).

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A live audio webcast of both the presentation and breakout session will be available on the Investors section of the Company’s website, www.alnylam.com. A replay will be available on the Alnylam website within 48 hours after the event.

On December 28, 2018 Agios Pharmaceuticals, Inc. (NASDAQ:AGIO), a leader in the field of cellular metabolism to treat cancer and rare genetic diseases, reported that the company is scheduled to present at the 37th Annual J.P. Morgan Healthcare Conference in San Francisco on Monday, January 7, 2019 at 9:30 a.m. PT (12:30 p.m. ET) (Press release, Agios Pharmaceuticals, DEC 28, 2018, View Source [SID1234532305]).

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A live webcast of the presentation can be accessed under "Events & Presentations" in the Investors section of the company’s website at www.agios.com. A replay of the webcast will be archived on the Agios website for at least two weeks following the presentation.

On December 24, 2018, Propanc Biopharma, Inc. (the "Company") reported that it entered into a securities purchase agreement (the "Eagle Purchase Agreement") with Eagle Equities, LLC ("Eagle Equities"), pursuant to which Eagle Equities purchased a convertible promissory note (the "December 2018 Eagle Note") from the Company in the aggregate principal amount of $126,000, such principal and the interest thereon convertible into shares of the Company’s common stock at the option of Eagle Equities any time after the six month anniversary of the December 2018 Eagle Note (Filing, 8-K, Propanc, DEC 28, 2018, View Source [SID1234532307]). The transactions contemplated by the Eagle Purchase Agreement closed on December 24, 2018. Pursuant to the terms of the Eagle Purchase Agreement, Eagle Equities deducted $6,000 from the principal payment due under the December 2018 Eagle Note, at the time of closing, to be applied to its legal expenses. The Company used the net proceeds from the December 2018 Eagle Note to repay an outstanding convertible promissory note before such note became convertible.

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The maturity date of the December 2018 Eagle Note is December 24, 2019. The December 2018 Eagle Note shall bear interest at a rate of 8% per annum, which interest shall be paid by the Company to Eagle Equities in shares of common stock upon receipt of a notice of conversion by the Company from Eagle Equities at any time after the six-month anniversary of the December 2018 Eagle Note.

Additionally, Eagle Equities has the option to convert all or any amount of the principal amount of the December 2018 Eagle Note, at any time, for shares of the Company’s common stock at a price equal to 61% of the lowest closing bid price (the "Closing Bid Price") of the Company’s common stock as reported on the OTC Markets Group, Inc. quotation system for the ten prior trading days, including the day upon which the Company receives a notice of conversion from Eagle Equities (the "Conversion Price"). However, in the event that the Company’s common stock is restricted by the Depository Trust Company for any reason, the Conversion Price shall be lowered to 51% of the lowest Closing Bid Price for the duration of such restriction. If the Company fails to maintain a reserve of shares of its common stock at least two and a half times the number of shares issuable upon conversion of the December 2018 Eagle Note for at least 60 days after the issuance of the December 2018 Eagle Note, the conversion discount shall be increased by 10%. Notwithstanding the foregoing, Eagle Equities shall be restricted from effecting a conversion if such conversion, along with other shares of the Company’s common stock beneficially owned by Eagle Equities and its affiliates, exceeds 4.99% of the outstanding shares of the Company’s common stock (which may be increased up to 9.9% upon 60 days’ prior written notice by Eagle Equities to the Company).

The December 2018 Eagle Note may be prepaid until June 22, 2019. If the December 2018 Eagle Note is prepaid within 90 days of the issuance date, then the prepayment premium shall be 115% of the principal amount plus any accrued interest; and if the December 2018 Eagle Note is prepaid after 90 days from the issuance date, but less than 181days from the issuance date, then the prepayment premium shall be 125% of the principal amount plus any accrued interest.

Upon a transfer of all or substantially all of the assets of the Company, or certain reorganization, merger or consolidation events, Eagle Equities may either request that the Company redeem the December 2018 Eagle Note in cash for 150% of the principal amount, plus any accrued but unpaid interest through the date of redemption, or convert the unpaid principal amount plus any accrued but unpaid interest into shares of the Company’s common stock at the Conversion Price.

The December 2018 Eagle Note contains certain events of default, including failure to timely issue shares upon receipt of a notice of conversion, as well as certain customary events of default, including, among others, a breach of the covenants, insolvency, bankruptcy and failure by the Company to pay the principal and interest due under the December 2018 Eagle Note.

Upon an event of default, interest on the outstanding principal shall accrue at a default interest rate of 24% per annum or at the highest rate permitted by law. In the event that the Company fails to deliver to Eagle Equities shares of common stock issuable upon conversion of principal or interest under the December 2018 Eagle Note within three business days of a notice of conversion by Eagle Equities (which includes an opinion of counsel), the Company shall incur liquidated damages of $250 per day the shares are not issued from the fourth to ninth business day after the notice is delivered to the Company and on the tenth day and thereafter, the liquidated damages shall increase to $500 per day.

Additional default penalties include: (i) in the event that the Company loses a bid price for its stock on its marketplace, the outstanding principal under the December 2018 Eagle Note shall increase by 20%; (ii) in the event that the Company’s common stock is delisted from any exchange or quotation system, or if its trading is suspending for more than ten consecutive days, or if the Company fails to meet its required reporting obligations under the Securities Exchange Act of 1934, as amended (the "Exchange Act"), the outstanding principal under the December 2018 Eagle Note shall increase by 50%; and (iii) in the event that the Company is delinquent in filing its periodic reports under the Exchange Act and such delinquency continues after the six month anniversary of the issuance date of the December 2018 Eagle Note, then Eagle Equities shall be entitled to use the lowest close bid price during the delinquency period as a base price for the conversion.

On December 27, 2018 Bio-Path Holdings, Inc., (NASDAQ: BPTH), a biotechnology company leveraging its proprietary DNAbilize antisense RNAi nanoparticle technology to develop a portfolio of targeted nucleic acid cancer drugs, reported an update from several clinical development programs and a 2019 business overview (Press release, Bio-Path Holdings, DEC 27, 2018, View Source [SID1234532290]).

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"Over the last year, we made solid progress across our growing development pipeline, highlighted by positive interim data from our Phase 2 study of prexigebersen in de novo acute myeloid leukemia (AML) patients," stated Peter H. Nielsen, chief executive officer of Bio-Path Holdings. "We enter 2019 focused and optimistic about our prospects for the clinical advancement of our pipeline of RNAi nanoparticle drugs in patients suffering from a variety of cancers of unmet medical need."

Phase 2 Study of Prexigebersen in De Novo AML Patients

In August 2018, Bio-Path announced first patient dosed in Stage 2 of the open-label Phase 2 study evaluating the efficacy and safety of prexigebersen (an antisense RNAi nanoparticle against Grb2 protein) in combination with LDAC and a second cohort of prexigebersen and decitabine, both therapeutic regimens well established in treatment of acute myeloid leukemia (AML) patients who cannot or elect not to be treated with more intensive chemotherapy. The primary objective of the study is to determine whether these combinations with prexigebersen provide greater efficacy than what would be expected with low-dose cytarabine (LDAC) or decitabine alone in this de novo patient population. In 2019, Bio-Path expects to open three trial sites in the EU, which Bio-Path expects will accelerate patient enrollment.

As previously announced, a planned interim analysis of Stage 1 of the study was performed on 17 evaluable patients, with four patients achieving complete responses (24%) and four patients achieving stable disease, including one patient achieving a morphologic leukemia free state and one patient who showed significantly reduced bone marrow blasts. In total, 47% of the evaluable patients showed some form of response, including stable disease, to the prexigebersen and LDAC combination treatment.

Efficacy data are encouraging in this challenging population in which the majority of patients had secondary AML or adverse-risk AML, and compares favorably to the reported CR (complete remission), CRp (complete remission with incomplete platelet recovery), and CRi (complete remission with incomplete hematologic recovery) rate with LDAC alone of 7-13%1.

Plans for a pivotal trial are expected to be discussed with the FDA if these results exceed expectations for current standard-of-care therapy.

Phase 2a Study of Prexigebersen in Accelerated and Blast Phase CML Patients

Bio-Path plans to continue enrolling patients in 2019 in a Phase 2a clinical study of prexigebersen in combination with the frontline therapy, dasatinib, for the treatment of chronic myeloid leukemia (CML) in accelerated and blast phase patients. For 2019, additional sites are planned to be added and enrollment planned to be opened across both phases of the disease, including imatinib-resistant chronic phase patients. The trial is currently being conducted at The University of Texas MD Anderson Cancer Center as a potential salvage therapy for accelerated and blast phase CML patients.

Two cohorts of three evaluable patients each are expected to be enrolled to evaluate two doses (60 mg/m2 and 90 mg/m2) of prexigebersen in combination with dasatinib.

Phase 1 Study of Prexigebersen in Patients with Advanced Solid Tumors

In 2019, Bio-Path intends to initiate a Phase 1 clinical trial of prexigebersen in patients with advanced solid tumors, including ovarian and uterine, pancreatic and hormone refractory breast cancer. This trial is expected to be conducted at several leading cancer centers and is planned to evaluate the safety of prexigebersen in combination with standard-of-care for each tumor type.

Phase 1 Study of BP1002 in Refractory or Relapsed Lymphoma Patients

Bio-Path expects to initiate a Phase 1 clinical trial of BP1002, an antisense RNAi nanoparticle targeting the Bcl-2 protein, in refractory or relapsed lymphoma and chronic lymphocytic leukemia (CLL) patients in 2019. The clinical trial is expected to be conducted at several premier cancer centers and is planned to evaluate the safety of BP1002 in several dose escalating cohorts to determine a maximum tolerated dose.

Preclinical Development of BP1003

The Company continues to advance its third investigation drug candidate, BP1003, for the treatment of advanced solid tumors, including pancreatic cancer. BP1003 is an antisense RNAi nanoparticle targeting the Stat3 protein. Bio-Path intends to initiate several Investigational New Drug application (IND) enabling studies for BP1003 in 2019.

1 Heiblig, Mediterr J Hematol 2016; Kantarjian, J Clin Oncol 2012; Dohner, Blood 2014.