ASLAN announced in July 2018 that it has received clinical trial authorisation in Singapore to conduct a Phase I study of ASLAN004 for the treatment of atopic dermatitis (AD). The product is a monoclonal antibody targeting interleukin 13 receptor α 1 (IL13Rα1). The Phase I dosing study will consist of a single dose escalation in healthy volunteers and a multiple dose escalation in AD patients.
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ASLAN Pharmaceuticals |
ASLAN004 a go for atopic dermatitis |
Clinical update |
Pharma & biotech |
9 July 2018 |
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ASLAN Pharmaceuticals is a research client of Edison Investment Research Limited |
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ASLAN announced in July 2018 that it has received clinical trial authorisation in Singapore to conduct a Phase I study of ASLAN004 for the treatment of atopic dermatitis (AD). The product is a monoclonal antibody targeting interleukin 13 receptor α 1 (IL13Rα1). The Phase I dosing study will consist of a single dose escalation in healthy volunteers and a multiple dose escalation in AD patients.
Year end |
Revenue ($m) |
PBT* |
EPS* |
DPS |
P/E |
Yield |
12/16 |
11.5 |
(7.6) |
(0.07) |
0.0 |
N/A |
N/A |
12/17 |
0.0 |
(38.8) |
(0.31) |
0.0 |
N/A |
N/A |
12/18e |
0.0 |
(38.9) |
(0.25) |
0.0 |
N/A |
N/A |
12/19e |
0.7 |
(62.5) |
(0.36) |
0.0 |
N/A |
N/A |
Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments.
ASLAN004 mechanism previously validated
The target of ASLAN004 IL13Rα1 is a subunit of an interleukin receptor on the surface of macrophages that regulates their inflammatory and anti-inflammatory properties. The principle of targeting this receptor has already been tested in the form of the drug Dupixent (dupilumab, Regeneron/Sanofi), which inhibits the receptor’s other subunit IL4Rα1. The drug was approved in March 2017 for atopic dermatitis and had revenues of €219m that year.
Atopic dermatitis: 18m adults affected in the US
AD is the most common form of eczema, affecting c 18 million adults in the US. Of these, 20% have moderate to severe disease and 4% have chronic forms, and we expect these patients to form the target market for the drug. The first-line treatment is typically topical steroids, although approximately half of patients with severe disease become refractory and require non-steroid treatments.
A competitive market
There are a number of options available for patients with steroid refractory AD both on the market and in development. Patients can be treated with PDE4 inhibitors such as Eucrisa (crisaborole, Pfizer) and calcineurin inhibitors such as Elidel (pimecrolimus, Valeant). In addition to Dupixent and ASLAN004, there are other drugs under development targeting the IL-4/IL-13 pathway such as tralokinumab (AstraZeneca) in Phase III and lebrikizumab (Dermira) in Phase 2b.
Valuation: Increased to $399m or $12.13 per ADS
We have increased our valuation to $399m or $12.13 per ADS from $364m or $11.04 per ADS due to the inclusion of ASLAN004. We arrive at a peak sales forecast of $587m based on conservative estimates of future market share (2%). The inclusion of the programme in our forecasts has increased our financing requirement by $22m to $82m, although we expect this to be offset by the out-licensing of assets.
ASLAN004 to enter Phase I
On 3 July 2018, ASLAN announced that it had submitted an application for clinical trial authorisation to the Singapore Health Science Authority to initiate a Phase I study of ASLAN004 for the treatment of atopic dermatitis (AD). It also provided a brief outline of the study which will consist of a single ascending dose portion in healthy volunteers and a multiple ascending dose portion in AD patients. We expect the trial to be initiated shortly after the application is approved (in our forecasts at the beginning of 2019). The dosing information found in this study can serve as the basis for further clinical study in the US and other geographies. The compound was licensed from CSL in 2014 and had a patent runway to 2027 (extendable to 2032).
ASLAN004 is an antibody that binds the interleukin 13 receptor α 1 (IL13Rα1), which is a receptor present on the surface of macrophages. This protein regulates the balance between the pro-inflammatory (M1) and anti-inflammatory (M2) states of the cell. This mechanism of action has already been validated by the approval of Dupixent (dupilumab, Regeneron/Sanofi), which was approved for the treatment of atopic dermatitis in 2017. Dupixent binds to IL4Rα, which is part of the same receptor complex as IL13Rα1, and generated revenues of €219m in its launch year. The drug has also been submitted for approval for severe asthma. AstraZeneca and Dermira also have programmes targeting this axis (Exhibit 1).
Exhibit 1: Programmes targeting IL-4/IL-13
Drug |
Company |
Target |
Development |
Dupixent (dupilumab) |
Regeneron/Sanofi |
anti-IL4Rα |
Approved |
Tralokinumab |
AstraZeneca |
anti-IL-13 |
Phase III |
Lebrikizumab |
Dermira |
anti-IL-13 |
Phase 2b |
ASLAN004 |
ASLAN |
anti-IL13Rα1 |
Phase I |
Source: EvaluatePharma
AD is the most common type of eczema, affecting an estimated 18 million adults in the US.1 Approximately 20% of these patients have moderate to severe disease necessitating medication, and approximately 4% develop a chronic form of the disease. If the condition is poorly controlled without medication, topical steroids are typically prescribed in the first line. However, about half of all patients with chronic disease become refractory to steroids, necessitating other pharmacological interventions, such as the PDE4 inhibitor Eucrisa (crisaborole, Pfizer) and calcineurin inhibitors such as Elidel (pimecrolimus, Valeant). We expect ASLAN004 to target a similar market of refractory moderate to severe patients.
National Eczema Association
Valuation
We have increased our valuation to $399m or $12.13 per ADS from $364m or $11.04 per ADS due to the inclusion of ASLAN004 in our models. We value the programme at $36m based on a relatively conservative 2% market share of chronic steroid refractory patients. We expect there to be substantial competition in the space among drugs targeting the IL-4/IL-13 axis as well as PDE4 inhibitors and others. Given the late entry of ASLAN004 to the market (launch in 2024), we remain conservative with our market share estimates. Despite this, we model a peak sales forecast of $587m. We expect pricing on par with Dupixent ($37,000 pa in 2017), adjusted for future price growth. The expected R&D programme is also based on Dupixent, with a total of 1,900 patients, although we expect a low cost of enrolment of $20,000 given the milder nature of the disease. Our probability of success for the programme is 15% because we have not seen any clinical data, although the mechanism of action has some validation through other programmes. Otherwise our valuation remains unchanged.
Exhibit 2: Valuation of ASLAN
Programme |
Indication |
Region |
Clinical stage |
Prob. of success |
Launch year |
Peak sales ($m) |
Margin/royalties (%) |
rNPV ($m) |
Varlitinib |
2nd line BTC |
US + Europe |
Phase II/III |
30% |
2020 |
277 |
59% |
121.6 |
East Asia |
Phase II/III |
30% |
2019-2020 |
195 |
53-58% |
73.9 |
||
R&D |
-7.2 |
|||||||
1st line GC |
US + Europe |
Phase II/III |
20% |
2021 |
182 |
57% |
31.8 |
|
East Asia |
Phase II/III |
20% |
2021 |
302 |
54-60% |
51.5 |
||
R&D |
-7.7 |
|||||||
Upfront and sales milestones payable |
-9.5 |
|||||||
ASLAN003 |
1st line AML |
US + Europe |
Phase II ready |
10% |
2022 |
308 |
59% |
38.0 |
R&D |
-4.0 |
|||||||
ASLAN002 Royalties |
1st line BC + GC |
US + Europe |
Phase II |
15% |
2022 |
909 |
5% |
16.9 |
ASLAN004 |
Refractory AD |
US + Europe |
Phase I |
15% |
2024 |
587 |
55% |
42.1 |
R&D |
-6.4 |
|||||||
Unallocated costs |
-11.8 |
|||||||
Total |
329.1 |
|||||||
Net cash and equivalents (Q118+ IPO + greenshoe) ($m) |
70.2 |
|||||||
Total firm value ($m) |
399.4 |
|||||||
Total basic ADSs (m) |
32.9 |
|||||||
Value per ADS ($) |
12.13 |
|||||||
Source: ASLAN reports, Edison Investment Research. Note: BTC=biliary tract cancer, GC=gastric cancer, AML=acute myeloid leukemia, AD=atopic dermatitis.
Financials
We have added the expected development costs of ASLAN004 to our financial projections, which has increased our financing requirements for the company. We expect the company to require $82m in additional capital before profitability in 2022, up from $60m previously. We expect this financing requirement to be met through the out-licensing of its products, including ASLAN004. However, in lieu of this agreement we record this as illustrative debt.
Exhibit 3: Financial summary
US$k |
2016 |
2017 |
2018e |
2019e |
||
31-December |
IFRS |
IFRS |
IFRS |
IFRS |
||
INCOME STATEMENT |
||||||
Revenue |
|
|
11,547 |
0 |
0 |
743 |
Cost of Sales |
(125) |
0 |
0 |
(111) |
||
Gross Profit |
11,422 |
0 |
0 |
631 |
||
R&D |
(13,165) |
(30,001) |
(30,526) |
(34,813) |
||
SG&A |
(6,956) |
(9,139) |
(10,966) |
(31,260) |
||
EBITDA |
|
|
(7,204) |
(37,803) |
(38,308) |
(62,113) |
Normalised operating profit |
|
|
(7,280) |
(38,013) |
(38,533) |
(62,337) |
Amortisation of acquired intangibles |
0 |
0 |
0 |
0 |
||
Exceptionals |
0 |
0 |
0 |
3 |
||
Share-based payments |
(1,420) |
(1,127) |
(2,959) |
(3,107) |
||
Reported operating profit |
(8,700) |
(39,140) |
(41,492) |
(65,441) |
||
Net Interest |
(477) |
(54) |
(198) |
(124) |
||
Joint ventures & associates (post tax) |
0 |
0 |
0 |
0 |
||
Exceptionals |
127 |
(699) |
(197) |
0 |
||
Profit Before Tax (norm) |
|
|
(7,629) |
(38,765) |
(38,929) |
(62,460) |
Profit Before Tax (reported) |
|
|
(9,049) |
(39,892) |
(41,888) |
(65,565) |
Reported tax |
0 |
0 |
0 |
0 |
||
Profit After Tax (norm) |
(7,629) |
(38,765) |
(38,929) |
(62,460) |
||
Profit After Tax (reported) |
(9,049) |
(39,892) |
(41,888) |
(65,565) |
||
Minority interests |
0 |
0 |
0 |
0 |
||
Discontinued operations |
0 |
0 |
0 |
0 |
||
Net income (normalised) |
(7,629) |
(38,765) |
(38,929) |
(62,460) |
||
Net income (reported) |
(9,049) |
(39,892) |
(41,888) |
(65,565) |
||
Basic average number of shares outstanding (m) |
105 |
124 |
157 |
175 |
||
EPS - basic normalised (US$) |
|
|
(0.07) |
(0.31) |
(0.25) |
(0.36) |
EPS - diluted normalised (US$) |
|
|
(0.07) |
(0.31) |
(0.25) |
(0.36) |
EPS - basic reported (US$) |
|
|
(0.09) |
(0.32) |
(0.27) |
(0.38) |
Dividend (US$) |
0.00 |
0.00 |
0.00 |
0.00 |
||
BALANCE SHEET |
||||||
Fixed Assets |
|
|
593 |
689 |
21,615 |
19,561 |
Intangible Assets |
84 |
84 |
21,053 |
18,999 |
||
Tangible Assets |
384 |
444 |
405 |
405 |
||
Investments & other |
125 |
161 |
158 |
158 |
||
Current Assets |
|
|
53,121 |
50,645 |
41,128 |
33,719 |
Stocks |
0 |
0 |
0 |
27 |
||
Debtors |
1,294 |
0 |
0 |
122 |
||
Cash & cash equivalents |
51,737 |
50,573 |
41,047 |
33,488 |
||
Other |
90 |
72 |
82 |
82 |
||
Current Liabilities |
|
|
(3,804) |
(5,979) |
(14,608) |
(7,161) |
Creditors |
(3,804) |
(5,979) |
(14,608) |
(7,161) |
||
Tax and social security |
0 |
0 |
0 |
0 |
||
Short term borrowings |
0 |
0 |
0 |
0 |
||
Other |
0 |
0 |
0 |
0 |
||
Long Term Liabilities |
|
|
(8,336) |
(9,841) |
(10,524) |
(70,966) |
Long term borrowings |
(8,336) |
(9,679) |
(10,099) |
(70,541) |
||
Other long term liabilities |
0 |
(162) |
(425) |
(425) |
||
Net Assets |
|
|
41,575 |
35,513 |
37,611 |
(24,846) |
Minority interests |
0 |
0 |
0 |
0 |
||
Shareholders' equity |
|
|
41,575 |
35,513 |
37,611 |
(24,846) |
CASH FLOW |
||||||
Op Cash Flow before WC and tax |
(7,204) |
(37,803) |
(38,308) |
(62,113) |
||
Working capital |
1,524 |
3,274 |
(2,325) |
4,204 |
||
Exceptional & other |
(109) |
(5) |
1,320 |
1,933 |
||
Tax |
0 |
0 |
0 |
0 |
||
Net operating cash flow |
|
|
(5,789) |
(34,534) |
(39,313) |
(55,975) |
Capex |
(374) |
(291) |
(195) |
(224) |
||
Acquisitions/disposals |
(81) |
(9) |
(11,801) |
(11,801) |
||
Net interest |
0 |
0 |
0 |
0 |
||
Equity financing |
31,364 |
33,061 |
42,320 |
0 |
||
Dividends |
0 |
0 |
0 |
0 |
||
Other |
(68) |
(36) |
0 |
0 |
||
Net Cash Flow |
25,052 |
(1,809) |
(8,989) |
(68,001) |
||
Opening net debt/(cash) |
|
|
0 |
(25,052) |
(22,544) |
(12,598) |
FX |
0 |
0 |
(979) |
0 |
||
Other non-cash movements |
0 |
(699) |
22 |
0 |
||
Closing net debt/(cash) |
|
|
(25,052) |
(22,544) |
(12,598) |
55,403 |
Source: ASLAN reports, Edison Investment Research
|
|
Circle actively manages its assets, placing an emphasis on total returns rather than short-term income maximisation. With three significant office refurbishments recently completed and in various stages of letting, it continues to harvest the benefit in terms of rising income and capital values, supporting growing dividends and NAV. FY18 NAV total return was 28.3% and, since the February 2016 IPO, the compound annual total return has been 26.2% pa. With a positive supply–demand balance in regional office markets continuing, we believe there are more gains to come.