Sunesis Pharmaceuticals — ASH 2018: 50mg cohort on last patient

Sunesis Pharmaceuticals — ASH 2018: 50mg cohort on last patient

The company provided an update at the American Society of Hematology (ASH) 2018 meeting in December on its ongoing dose-escalation study of vecabrutinib for B-cell malignancies. Four new patients have been enrolled in the past month and the 50 mg cohort is now overenrolled. Safety data is only needed from a single patient, so barring any issues, the trial should progress to 100mg soon, where we may see the first signs of efficacy.

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Sunesis Pharmaceuticals

ASH 2018: 50mg cohort on last patient

Clinical update

Pharma & biotech

10 December 2018

Price

US$0.46

Market cap

US$17m

Net cash ($m) at Q318

12.8

Shares in issue

37.4m

Free float

96%

Code

SNSS

Primary exchange

NASDAQ

Secondary exchange

N/A

Share price performance

%

1m

3m

12m

Abs

(66.0)

(78.8)

(78.9)

Rel (local)

(63.7)

(76.8)

(78.9)

52-week high/low

US$7.4

US$0.4

Business description

Sunesis Pharmaceuticals is a pharmaceutical company focused on oncology. Its lead asset is SNS-062, a Bruton’s tyrosine kinase inhibitor for chronic lymphocytic leukemia for Imbruvica-refractory patients. The program is entering a dose escalation Phase Ib/II. It has also developed TAK-580 with partner Takeda, and the preclinical PDK1 inhibitor SNS-510.

Next events

Progress to 100mg cohort

Upcoming

SNS-510 IND filing

2019

Analysts

Nathaniel Calloway

+1 646 653 7036

Maxim Jacobs

+1 646 653 7027

Sunesis Pharmaceuticals is a research client of Edison Investment Research Limited

The company provided an update at the American Society of Hematology (ASH) 2018 meeting in December on its ongoing dose-escalation study of vecabrutinib for B-cell malignancies. Four new patients have been enrolled in the past month and the 50 mg cohort is now overenrolled. Safety data is only needed from a single patient, so barring any issues, the trial should progress to 100mg soon, where we may see the first signs of efficacy.

Year end

Revenue ($m)

PBT*
($m)

EPS*
($)

DPS
($)

P/E
(x)

Yield
(%)

12/16

2.5

(38.0)

(2.42)

0.00

N/A

N/A

12/17

0.7

(35.5)

(1.45)

0.00

N/A

N/A

12/18e

0.2

(28.8)

(0.81)

0.00

N/A

N/A

12/19e

0.0

(34.9)

(0.94)

0.00

N/A

N/A

Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments.

Signs of forward progress

The dosing study has struggled to progress past the 50mg cohort with delays due to a cohort expansion and patients that progressed before safety could be evaluated. However, following these most recent results it may soon be in the rear view. Enrolment appears to progressing steadily across the eight open clinical sites, and there are four patients on the drug after the enrolment, including two new patients in the 50mg cohort (although only one is needed to progress).

AEs in line, GI effects limited to date

The company presented the most detailed data so far on adverse events (AEs) from the 10 patients that were evaluable for safety. The most common continue to be hematological, which is normal for this drug class and patient population. Interestingly, there have been few gastrointestinal (GI) AEs, which is unlike what has been previously seen with Imbruvica and Calquence. It remains too early to draw definitive conclusions, but it would be a substantial benefit if vecabrutinib lacked the GI effects of these other drugs.

Vecabrutinib inhibits pBTK and downstream effects

The company also provided new data on the pharmacokinetics (PK) and pharmacodynamics of the drug in the patients it examined. PK remains consistent with previous results and in line with twice a day (BID) dosing. The company also provide data demonstrating that the drug inhibited the generation of phosphorylated Bruton’s tyrosine kinase (pBTK), which is the mechanism of action of this class. Finally, the company showed that the drug inhibited the generation of cytokines in these patients, which is the downstream effect of BTK inhibition. This provides evidence indicating a definitive drug effect in these patients.

Valuation: Unchanged at $224m or $5.99 per share

Our valuation remains unchanged at $224m or $5.99 fper basic share. We expect to update this following additional data from the ongoing study. We expect the company to require at $135m in financing before profitability in 2023.

The 50mg cohort overenrolled at ASH 2018

Sunesis presented a poster at ASH (followed up with a detailed presentation) on 2 December 2018 that provided an update on the progress of the company in its Phase Ib/II trial of vecabrutinib. The drug is an oral non-covalent BTK inhibitor being examined for chronic lymphocytic leukemia (CLL) and other B-cell malignancies. The data in the poster and presentation is consistent with the previous data provided in the abstract, but provides a to-the-minute look into the progress of the trial and an additional level of detail.

Importantly, the company announced it recently enrolled two additional patients into its 50mg BID dosing arm since the poster went to press, overenrolling it. Five of the six required patients have completed their safety evaluation, so only a single additional safety readout is needed before advancing to the next dose. A total of 13 patients have been enrolled to date, an increase of four since the abstract of the poster was presented. The company has faced a series of events that stalled completion of this cohort, so it is good to see progress continuing. Previously, an ALT elevation prevented a patient from receiving a number of doses, triggering a cohort expansion to six patients (per the standard 3+3 dose escalation protocol). Of the new patients, three progressed before they could be evaluated. We view these events as unfortunate and not necessarily indicative of any issues with the drug. The 50mg cohort is below the expected efficacy threshold at 100mg BID or higher, so we expect future cohorts to provide a clearer picture of the drug’s safety and efficacy profile. For the current report, 11 patients were evaluable in some fashion.

The company provided a detailed breakdown of the AE profile from the 10 patients with data available (Exhibit 1). As previously described, hematologic AEs were common but are not unusual for this class of drug or this patient population. Four grade three events that were potentially related to drug were observed, three hematologic and the third being the previously mentioned ALT elevation. Of note in this profile is that the rate of GI events is low. This is in contrast to Imbruvica, which has high rates of GI effects (51% diarrhea, 31% nausea, 25% constipation, etc). Calquence also has high rates of reported GI effects, albeit at lower levels than Imbruvica. This indicates that the AE profile of vecabrutinib may be significantly different than these drugs, although higher doses will need to be evaluated before drawing any definitive conclusions.

Exhibit 1: Vecabrutinib dose-escalation safety

Source: Sunesis

The company also provided additional PK and pharmacodynamic data to support the proposition of vecabrutinib. The PKs in the trial appear similar to previous in vivo measurements. The company also provided a breakdown of the impact of vecabrutinib on the concentrations of pBTK (Exhibit 2). pBTK is the active form of the enzyme and the efficacy of BTK inhibitors is effected by reductions in its concentration. These data also include patients with a C481 mutation, which is inadequately treated by Imbruvica. Moreover, the company provided evidence that the drug was having an impact on B-cell function, as indicated by a reduction in cytokines measured in a selection of patients (Exhibit 3). These data provide evidence that the drug is working as intended, and having a physiological impact.

Exhibit 2: Inhibition of pBTK production

Exhibit 3: Reduction in cytokines

Source: Sunesis

Source: Sunesis

Exhibit 2: Inhibition of pBTK production

Source: Sunesis

Exhibit 3: Reduction in cytokines

Source: Sunesis

Based on these data we expect the upcoming cohorts to provide data on the efficacy of the drug. The company noted that early indications of drug effect were seen but it did not report any measures of efficacy in this data. There are eight sites enrolling patients, and the company signalled that it believed these would be sufficient. Of the 13 patients enrolled to date, the majority (nine) had CLL. Patients with mantle cell lymphoma and Waldenstrom macroglobulinemia have also been enrolled in the trial, and earlier this year the company expanded enrolment to include other B-cell malignancies such as diffuse large B-cell lymphoma and follicular lymphoma (although the company did not report any of these patients in the 11 that were evaluable). The company also announced in its presentation that it would be further expanding its enrolment to include marginal zone lymphoma in the near future. Marginal zone lymphoma is the third most common form of non-Hodgkin lymphoma (NHL), and data in this population could provide increasing evidence of utility in the NHL population, as well as potentially improve enrolment.

In other ASH news

Arqule is also developing a non-covalent BTK inhibitor ARQ-531, on which it presented data at ASH. ARQ-531 is also in a dose escalation study and is enrolling its seventh cohort. The main insight from the company’s poster is that it observed its first partial response (PR) in a patient with follicular lymphoma. It is worth noting the study is in a dosing range where responses are expected (according to management), but the PR in question occurred after a patient had an unexpected response to much lower doses. Additionally, no PRs have been observed yet in the main indication of CLL.

Aptose Biosciences provided some initial preclinical data on its non-covalent FLT3/BTK inhibitor CG’806. FLT3 is a protein frequently mutated in B-cell malignancies, and the idea of this program is that the combined inhibition of both FLT3 and BTK will provide more potent effects. The drug was compared to Imbruvica in a range of cell lines and primary tumor cells, where is significantly higher cytostatic and cytotoxic potency shown. We plan to see in the future if this drug has the other properties besides potency necessary for effective treatment. Aptose has said it plans to file an IND in 2019.

Valuation

Our valuation remains unchanged at $224m or $5.99 per basic share and we have not updated our model. The timing for the progression through the 50mg cohort is in line with our expectations. We may update the valuation in future when further data are released from the ongoing clinical study.

Exhibit 4: Valuation of Sunesis

Development program

Clinical stage

Expected commercialization

Prob. of success

Launch year

Launch Pricing ($)

Peak sales ($m)

Patent/exclusivity protection

Royalty/ margin

rNPV ($m)

TAK-580

Phase I/II

Licensed to Takeda

10%

2025

500,000

603

2032

15%

19

Vecabrutinib

Phase Ib/II

Proprietary

20%

2023

152,000

666

2034

56%

187

SNS-510

IND ready

Proprietary

10%

2024

130,000

361

2031

51%

25

Unallocated costs (discovery programs, administrative costs, etc.)

(20)

Total

 

 

 

 

 

 

 

 

211

Net cash and equivalents (Q318) ($m)

12.8

Total firm value ($m)

224.0

Total basic shares (m)

37.4

Value per basic share ($)

5.99

Convertible pref stock (m)

6.3

Warrants and options

8.7

Total diluted shares (m)

52.4

Value per diluted share ($)

4.98

Source: Sunesis reports, Edison Investment Research

Financials

Our financial projections also remain unchanged. The company ended Q318 with $20m in cash (and $7.3m in debt). Burn rates have historically been between $5m and $7m per quarter, so we expect the company to need additional financing in the near term. We currently model $25m in financing (as illustrative debt) in 2018, although we may move this into early 2019 depending on internal timelines. We expect the company to require a total of $135m in financing before profitability in 2023 ($25m, $20m, $30m, $40m and $20m in 2018–2022 respectively).

Exhibit 5: Financial summary

$'000s

2016

2017

2018e

2019e

Year end 31 December

US GAAP

US GAAP

US GAAP

US GAAP

PROFIT & LOSS

Revenue

 

 

2,536

669

237

0

Cost of Sales

0

0

0

0

Gross Profit

2,536

669

237

0

Research and development

(22,881)

(21,540)

(15,123)

(17,485)

Selling, general & administrative

(16,115)

(13,548)

(12,575)

(12,952)

EBITDA

 

 

(36,313)

(34,428)

(27,470)

(30,447)

Operating Profit (before GW and except.)

(36,302)

(34,419)

(27,461)

(30,438)

Intangible Amortisation

0

0

0

0

Exceptionals/Other

0

0

0

0

Operating Profit

(36,302)

(34,419)

(27,461)

(30,438)

Net Interest

(1,721)

(1,039)

(1,360)

(4,475)

Other (change in fair value of warrants)

0

0

0

0

Profit Before Tax (norm)

 

 

(38,023)

(35,458)

(28,821)

(34,912)

Profit Before Tax (IFRS)

 

 

(38,023)

(35,458)

(28,821)

(34,912)

Tax

0

0

0

0

Deferred tax

0

0

0

0

Profit After Tax (norm)

(38,023)

(35,458)

(28,821)

(34,912)

Profit After Tax (IFRS)

(38,023)

(35,458)

(28,821)

(34,912)

Average Number of Shares Outstanding (m)

15.7

24.5

35.6

37.2

EPS - normalised ($)

 

 

(2.42)

(1.45)

(0.81)

(0.94)

EPS - IFRS ($)

 

 

(2.42)

(1.45)

(0.81)

(0.94)

Dividend per share ($)

0.0

0.0

0.0

0.0

BALANCE SHEET

Fixed Assets

 

 

3

1,401

11

2

Intangible Assets

0

0

0

0

Tangible Assets

3

20

11

2

Other

0

1,381

0

0

Current Assets

 

 

43,231

32,933

38,989

28,318

Stocks

0

0

0

0

Debtors

0

0

0

0

Cash

42,588

31,750

37,687

27,016

Other

643

1,183

1,302

1,302

Current Liabilities

 

 

(5,814)

(8,901)

(1,414)

(1,554)

Creditors

(2,481)

(1,697)

(1,414)

(1,554)

Short term borrowings

(3,333)

(7,204)

0

0

Long Term Liabilities

 

 

(11,271)

(112)

(32,400)

(52,400)

Long term borrowings

(11,102)

0

(32,396)

(52,396)

Other long term liabilities

(169)

(112)

(4)

(4)

Net Assets

 

 

26,149

25,321

5,186

(25,634)

CASH FLOW

Operating Cash Flow

 

 

(36,962)

(36,142)

(25,373)

(30,671)

Net Interest

0

0

0

0

Tax

0

0

0

0

Capex

0

(26)

0

0

Acquisitions/disposals

0

0

0

0

Financing

26,111

32,930

6,303

0

Dividends

0

0

0

0

Other

0

0

0

0

Net Cash Flow

(10,851)

(3,238)

(19,070)

(30,671)

Opening net debt/(cash)

 

 

(38,596)

(28,153)

(24,546)

(5,291)

HP finance leases initiated

0

0

0

0

Exchange rate movements

0

0

0

0

Other

408

(369)

(185)

0

Closing net debt/(cash)

 

 

(28,153)

(24,546)

(5,291)

25,380

Source: Sunesis reports, Edison Investment Research

General disclaimer and copyright

This report has been commissioned by Sunesis Pharmaceuticals and prepared and issued by Edison, in consideration of a fee payable by Sunesis Pharmaceuticals. Edison Investment Research standard fees are £49,500 pa for the production and broad dissemination of a detailed note (Outlook) following by regular (typically quarterly) update notes. Fees are paid upfront in cash without recourse. Edison may seek additional fees for the provision of roadshows and related IR services for the client but does not get remunerated for any investment banking services. We never take payment in stock, options or warrants for any of our services.

Accuracy of content: All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report and have not sought for this information to be independently verified. Opinions contained in this report represent those of the Edison analyst at the time of publication. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations.

Exclusion of Liability: To the fullest extent allowed by law, Edison shall not be liable for any direct, indirect or consequential losses, loss of profits, damages, costs or expenses incurred or suffered by you arising out or in connection with the access to, use of or reliance on any information contained on this note.

No personalised advice: The information that we provide should not be construed in any manner whatsoever as, personalised advice. Also, the information provided by us should not be construed by any subscriber or prospective subscriber as Edison’s solicitation to effect, or attempt to effect, any transaction in a security. The securities described in the report may not be eligible for sale in all jurisdictions or to certain categories of investors.

Investment in securities mentioned: Edison has a restrictive policy relating to personal dealing and conflicts of interest. Edison Group does not conduct any investment business and, accordingly, does not itself hold any positions in the securities mentioned in this report. However, the respective directors, officers, employees and contractors of Edison may have a position in any or related securities mentioned in this report, subject to Edison's policies on personal dealing and conflicts of interest.

Copyright: Copyright 2018 Edison Investment Research Limited (Edison). All rights reserved FTSE International Limited (“FTSE”) © FTSE 2018. “FTSE®” is a trade mark of the London Stock Exchange Group companies and is used by FTSE International Limited under license. All rights in the FTSE indices and/or FTSE ratings vest in FTSE and/or its licensors. Neither FTSE nor its licensors accept any liability for any errors or omissions in the FTSE indices and/or FTSE ratings or underlying data. No further distribution of FTSE Data is permitted without FTSE’s express written consent.

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Edison Investment Research Pty Ltd (Edison AU) is the Australian subsidiary of Edison. Edison AU is a Corporate Authorised Representative (1252501) of Myonlineadvisers Pty Ltd who holds an Australian Financial Services Licence (Number: 427484). This research is issued in Australia by Edison AU and any access to it, is intended only for "wholesale clients" within the meaning of the Corporations Act 2001 of Australia. Any advice given by Edison AU is general advice only and does not take into account your personal circumstances, needs or objectives. You should, before acting on this advice, consider the appropriateness of the advice, having regard to your objectives, financial situation and needs. If our advice relates to the acquisition, or possible acquisition, of a particular financial product you should read any relevant Product Disclosure Statement or like instrument.

New Zealand

The research in this document is intended for New Zealand resident professional financial advisers or brokers (for use in their roles as financial advisers or brokers) and habitual investors who are “wholesale clients” for the purpose of the Financial Advisers Act 2008 (FAA) (as described in sections 5(c) (1)(a), (b) and (c) of the FAA). This is not a solicitation or inducement to buy, sell, subscribe, or underwrite any securities mentioned or in the topic of this document. For the purpose of the FAA, the content of this report is of a general nature, is intended as a source of general information only and is not intended to constitute a recommendation or opinion in relation to acquiring or disposing (including refraining from acquiring or disposing) of securities. The distribution of this document is not a “personalised service” and, to the extent that it contains any financial advice, is intended only as a “class service” provided by Edison within the meaning of the FAA (i.e. without taking into account the particular financial situation or goals of any person). As such, it should not be relied upon in making an investment decision.

United Kingdom

Neither this document and associated email (together, the "Communication") constitutes or form part of any offer for sale or subscription of, or solicitation of any offer to buy or subscribe for, any securities, nor shall it or any part of it form the basis of, or be relied on in connection with, any contract or commitment whatsoever. Any decision to purchase shares in the Company in the proposed placing should be made solely on the basis of the information to be contained in the admission document to be published in connection therewith.

This Communication is being distributed in the United Kingdom and is directed only at (i) persons having professional experience in matters relating to investments, i.e. investment professionals within the meaning of Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "FPO") (ii) high net-worth companies, unincorporated associations or other bodies within the meaning of Article 49 of the FPO and (iii) persons to whom it is otherwise lawful to distribute it. The investment or investment activity to which this document relates is available only to such persons. It is not intended that this document be distributed or passed on, directly or indirectly, to any other class of persons and in any event and under no circumstances should persons of any other description rely on or act upon the contents of this document (nor will such persons be able to purchase shares in the placing).

This Communication is being supplied to you solely for your information and may not be reproduced by, further distributed to or published in whole or in part by, any other person.

United States

The Investment Research is a publication distributed in the United States by Edison Investment Research, Inc. Edison Investment Research, Inc. is registered as an investment adviser with the Securities and Exchange Commission. Edison relies upon the "publishers' exclusion" from the definition of investment adviser under Section 202(a) (11) of the Investment Advisers Act of 1940 and corresponding state securities laws. This report is a bona fide publication of general and regular circulation offering impersonal investment-related advice, not tailored to a specific investment portfolio or the needs of current and/or prospective subscribers. As such, Edison does not offer or provide personal advice and the research provided is for informational purposes only. No mention of a particular security in this report constitutes a recommendation to buy, sell or hold that or any security, or that any particular security, portfolio of securities, transaction or investment strategy is suitable for any specific person.

Frankfurt +49 (0)69 78 8076 960

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Frankfurt +49 (0)69 78 8076 960

Schumannstrasse 34b

60325 Frankfurt

Germany

London +44 (0)20 3077 5700

280 High Holborn

London, WC1V 7EE

United Kingdom

New York +1 646 653 7026

295 Madison Avenue, 18th Floor

10017, New York

US

Sydney +61 (0)2 8249 8342

Level 4, Office 1205

95 Pitt Street, Sydney

NSW 2000, Australia

General disclaimer and copyright

This report has been commissioned by Sunesis Pharmaceuticals and prepared and issued by Edison, in consideration of a fee payable by Sunesis Pharmaceuticals. Edison Investment Research standard fees are £49,500 pa for the production and broad dissemination of a detailed note (Outlook) following by regular (typically quarterly) update notes. Fees are paid upfront in cash without recourse. Edison may seek additional fees for the provision of roadshows and related IR services for the client but does not get remunerated for any investment banking services. We never take payment in stock, options or warrants for any of our services.

Accuracy of content: All information used in the publication of this report has been compiled from publicly available sources that are believed to be reliable, however we do not guarantee the accuracy or completeness of this report and have not sought for this information to be independently verified. Opinions contained in this report represent those of the Edison analyst at the time of publication. Forward-looking information or statements in this report contain information that is based on assumptions, forecasts of future results, estimates of amounts not yet determinable, and therefore involve known and unknown risks, uncertainties and other factors which may cause the actual results, performance or achievements of their subject matter to be materially different from current expectations.

Exclusion of Liability: To the fullest extent allowed by law, Edison shall not be liable for any direct, indirect or consequential losses, loss of profits, damages, costs or expenses incurred or suffered by you arising out or in connection with the access to, use of or reliance on any information contained on this note.

No personalised advice: The information that we provide should not be construed in any manner whatsoever as, personalised advice. Also, the information provided by us should not be construed by any subscriber or prospective subscriber as Edison’s solicitation to effect, or attempt to effect, any transaction in a security. The securities described in the report may not be eligible for sale in all jurisdictions or to certain categories of investors.

Investment in securities mentioned: Edison has a restrictive policy relating to personal dealing and conflicts of interest. Edison Group does not conduct any investment business and, accordingly, does not itself hold any positions in the securities mentioned in this report. However, the respective directors, officers, employees and contractors of Edison may have a position in any or related securities mentioned in this report, subject to Edison's policies on personal dealing and conflicts of interest.

Copyright: Copyright 2018 Edison Investment Research Limited (Edison). All rights reserved FTSE International Limited (“FTSE”) © FTSE 2018. “FTSE®” is a trade mark of the London Stock Exchange Group companies and is used by FTSE International Limited under license. All rights in the FTSE indices and/or FTSE ratings vest in FTSE and/or its licensors. Neither FTSE nor its licensors accept any liability for any errors or omissions in the FTSE indices and/or FTSE ratings or underlying data. No further distribution of FTSE Data is permitted without FTSE’s express written consent.

Australia

Edison Investment Research Pty Ltd (Edison AU) is the Australian subsidiary of Edison. Edison AU is a Corporate Authorised Representative (1252501) of Myonlineadvisers Pty Ltd who holds an Australian Financial Services Licence (Number: 427484). This research is issued in Australia by Edison AU and any access to it, is intended only for "wholesale clients" within the meaning of the Corporations Act 2001 of Australia. Any advice given by Edison AU is general advice only and does not take into account your personal circumstances, needs or objectives. You should, before acting on this advice, consider the appropriateness of the advice, having regard to your objectives, financial situation and needs. If our advice relates to the acquisition, or possible acquisition, of a particular financial product you should read any relevant Product Disclosure Statement or like instrument.

New Zealand

The research in this document is intended for New Zealand resident professional financial advisers or brokers (for use in their roles as financial advisers or brokers) and habitual investors who are “wholesale clients” for the purpose of the Financial Advisers Act 2008 (FAA) (as described in sections 5(c) (1)(a), (b) and (c) of the FAA). This is not a solicitation or inducement to buy, sell, subscribe, or underwrite any securities mentioned or in the topic of this document. For the purpose of the FAA, the content of this report is of a general nature, is intended as a source of general information only and is not intended to constitute a recommendation or opinion in relation to acquiring or disposing (including refraining from acquiring or disposing) of securities. The distribution of this document is not a “personalised service” and, to the extent that it contains any financial advice, is intended only as a “class service” provided by Edison within the meaning of the FAA (i.e. without taking into account the particular financial situation or goals of any person). As such, it should not be relied upon in making an investment decision.

United Kingdom

Neither this document and associated email (together, the "Communication") constitutes or form part of any offer for sale or subscription of, or solicitation of any offer to buy or subscribe for, any securities, nor shall it or any part of it form the basis of, or be relied on in connection with, any contract or commitment whatsoever. Any decision to purchase shares in the Company in the proposed placing should be made solely on the basis of the information to be contained in the admission document to be published in connection therewith.

This Communication is being distributed in the United Kingdom and is directed only at (i) persons having professional experience in matters relating to investments, i.e. investment professionals within the meaning of Article 19(5) of the Financial Services and Markets Act 2000 (Financial Promotion) Order 2005, as amended (the "FPO") (ii) high net-worth companies, unincorporated associations or other bodies within the meaning of Article 49 of the FPO and (iii) persons to whom it is otherwise lawful to distribute it. The investment or investment activity to which this document relates is available only to such persons. It is not intended that this document be distributed or passed on, directly or indirectly, to any other class of persons and in any event and under no circumstances should persons of any other description rely on or act upon the contents of this document (nor will such persons be able to purchase shares in the placing).

This Communication is being supplied to you solely for your information and may not be reproduced by, further distributed to or published in whole or in part by, any other person.

United States

The Investment Research is a publication distributed in the United States by Edison Investment Research, Inc. Edison Investment Research, Inc. is registered as an investment adviser with the Securities and Exchange Commission. Edison relies upon the "publishers' exclusion" from the definition of investment adviser under Section 202(a) (11) of the Investment Advisers Act of 1940 and corresponding state securities laws. This report is a bona fide publication of general and regular circulation offering impersonal investment-related advice, not tailored to a specific investment portfolio or the needs of current and/or prospective subscribers. As such, Edison does not offer or provide personal advice and the research provided is for informational purposes only. No mention of a particular security in this report constitutes a recommendation to buy, sell or hold that or any security, or that any particular security, portfolio of securities, transaction or investment strategy is suitable for any specific person.

Frankfurt +49 (0)69 78 8076 960

Schumannstrasse 34b

60325 Frankfurt

Germany

London +44 (0)20 3077 5700

280 High Holborn

London, WC1V 7EE

United Kingdom

New York +1 646 653 7026

295 Madison Avenue, 18th Floor

10017, New York

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Research: Healthcare

CASI Pharmaceuticals — Evomela approved in China

CASI announced that it has received approval in China for Evomela. The drug is a formulation of melphalan hydrochloride used in the treatment of multiple myeloma, and CASI obtained the rights to the drug in Greater China from its original developer, Spectrum Pharmaceuticals, in 2014. This put CASI in a unique position to take advantage of the regulatory reforms in China. The drug was approved under the new priority review pathway at the National Medical Products Administration (NMPA, formerly the CFDA) and serves as a test case for this new regulatory regime.

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