Bionomics announced on 23 May 2018 it has initiated a Phase IIa study of its α7 nicotinic receptor inhibitor for the treatment of agitation in the elderly in a hospital setting. Agitation is a common problem (13-24%) in patients with dementia, and we expect the trial to focus primarily on this population. It will enrol a target of 40 patients across Australia and is expected to provide top-line data in calendar Q119.
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Bionomics |
Phase IIa in agitation of the elderly initiated |
Clinical update |
Pharma & biotech |
29 May 2018 |
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Bionomics announced on 23 May 2018 it has initiated a Phase IIa study of its α7 nicotinic receptor inhibitor for the treatment of agitation in the elderly in a hospital setting. Agitation is a common problem (13-24%) in patients with dementia, and we expect the trial to focus primarily on this population. It will enrol a target of 40 patients across Australia and is expected to provide top-line data in calendar Q119.
Year end |
Revenue (A$m) |
PBT* |
EPS* |
DPS |
P/E |
Yield |
06/16 |
8.1 |
(16.7) |
(0.04) |
0.00 |
N/A |
N/A |
06/17 |
18.6 |
(4.4) |
(0.01) |
0.00 |
N/A |
N/A |
06/18e |
17.5 |
(7.1) |
(0.01) |
0.00 |
N/A |
N/A |
06/19e |
5.1 |
(28.4) |
(0.05) |
0.00 |
N/A |
N/A |
Note: *PBT and EPS are normalised, excluding amortisation of acquired intangibles, exceptional items and share-based payments.
Significant need with poor options
Agitation in patients with Alzheimer’s disease and other forms of dementia is a significant burden on the healthcare system because of the increased needs of these patients. One study estimated costs of £29,000 to £57,000 per affected patient per year in the UK. Moreover, pharmacologic treatment options are limited to benzodiazepines; these are sedating and anti-psychotics, which have a black-box warning for increased mortality in these patients.
Novel mechanism may provide a solution
BNC210 holds the potential for being a non-sedating anxiolytic, thereby potentially enabling it to be used in patients with agitation both in the acute and chronic setting. The company previously presented data from its Phase II anxiety study showing that the drug inhibited the activation of the amygdalae, a region of the brain rich in α7 receptor and associated with fear and emotional responses, which points to the potential utility of this drug for the treatment of agitation.
Posttraumatic stress disorder fully enrolled
In April 2018 the company announced that its Phase IIb study of BNC210 in posttraumatic stress disorder (PTSD) was fully enrolled and on schedule to report top-line results in calendar H218. The trial has 193 patients being observed over 12 weeks, with the primary outcome as improvement in the functional PTSD symptom rating, Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).
Valuation: Increased to A$492m or A$1.02
We have increased our valuation of Bionomics to A$492m or A$1.02 per basic share from A$418.7m or A$0.87 per basic share. This increase is largely driven by the inclusion of the agitation indication in our models (A$47.6m) with a 20% probability of success. Additionally the increase is driven by rolling forward our NPVs to the most recent period. The company ended fiscal Q318 with A$32.3m in cash and A$19.4m in debt.
Expanding BNC210 into agitation
On 23 May 2018 Bionomics announced that it had initiated a clinical study of BNC210 for the treatment of agitation in the elderly in a hospital setting. Agitation is a common neuropsychiatric symptom typically associated with dementia. Agitation in this population represents a significant burden on the healthcare system. There are 1.4 million patients in nursing home care in the US, of which approximately 80% have dementia of some form (predominantly Alzheimer’s disease). One report estimated the prevalence of agitation at between 13% and 24% at any given time in dementia patients.1 A study examining the costs of agitation in British Alzheimer’s disease patients found costs of £29,000 to £57,000 per affected patient per year in the form of increased health and social care costs.2
Steinberg M, et al. (2008) Point and 5-year period prevalence of neuropsychiatric symptoms in dementia: the Cache County Study. Int J Geriatr Psychiatry 23, 170-177.
Morris S, et al. (2015) Monetary costs of agitation in older adults with Alzheimer's disease in the UK: prospective cohort study. Brit J Med Open 5, e007382.
Unfortunately, there are limited options for the treatment of dementia-related agitation. There are no approved medications for this indication. Benzodiazepines can be used for the short-term alleviation of symptoms but, given their sedating effects and the development of tolerance, they are not generally considered appropriate for long-term treatment. Anti-depressants such as SSRIs can be prescribed for patients with depression, which is common in dementia patients, and frequently have agitation as a comorbidity. Anti-psychotics can be helpful in alleviating underlying psychosis, which may be a causative factor in agitation, and these agents have gained the most widespread use of pharmacologic treatments. However, all antipsychotics carry a black-box warning for the treatment of dementia patients because their use is associated with increased mortality.
BNC210’s novel mechanism of action positions it as a potential solution to the limitations associated with other pharmaceutical treatments. It has anxiolytic activity, which may provide acute relief from symptoms, similar to benzodiazepines but without the sedating side effects that limit routine use. Moreover, the company previously demonstrated in its Phase IIa study that BNC210 reduces the activation of the amygdalae (Exhibit 1), a region of the brain associated with fear and emotion. One manifestation in this study (among others) was decreased threat avoidance behaviour in the Joystick Operated Runway Task (JORT) (Exhibit 2). It is therefore plausible that the drug may reduce emotional arousal in dementia patients.
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Exhibit 1: Reduction in amygdala activation from low-dose BNC210 |
Exhibit 2: Threat avoidance behaviour in the JORT |
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Source: Bionomics. Note: *p<0.05. |
Source: Bionomics. Note: *p<0.05, **p<0.01. |
|
Exhibit 1: Reduction in amygdala activation from low-dose BNC210 |
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|
Source: Bionomics. Note: *p<0.05. |
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Exhibit 2: Threat avoidance behaviour in the JORT |
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Source: Bionomics. Note: *p<0.05, **p<0.01. |
The Phase IIa study will be randomized, double-blind and placebo controlled. Approximately 40 patients from geriatric hospital wards in Australia will be enrolled and monitored over a five-day treatment and a two-day follow-up period. Based on these parameters, the study should be quick, and the company expects to report results in Q1 of calendar year 2019. The primary endpoint of the study will be improvement in agitation symptoms as measured on the Pittsburgh Agitation Scale (PAS). The PAS is a 16-point assessment over four behaviour groups: vocalization (complaints, yelling), motor agitation (pacing, banging), aggressiveness (threats, violent gestures) and resisting care. Secondary endpoints for the study include safety and tolerability and improvement in clinical global impression scale (CGI-I).
PTSD trial fully enrolled
In April 2018, the company reported that it had fully enrolled its Phase II PTSD study. The study was designed for enrolment of up to 192 patients. 193 patients were enrolled and are being monitored over the course of 12 weeks. The primary endpoint of the study is improvement in CAPS-5, with secondary endpoints of impact of the drug on individual symptom clusters of the CAPS-5 (arousal and reactivity, avoidance, negative alterations in cognition and mood, intrusion symptoms), anxiety using the Hamilton Anxiety Rating Scale and on depression using the Montgomery-Asberg Depression Rating Scale. Given the range of effects being investigated, we expect the data from this study to be rich and to inform future clinical directions outside of PTSD. The company announced that top-line results are expected in H2 of calendar year 2018.
Valuation
We have increased our valuation of Bionomics to A$492m or A$1.02 per basic share from A$418.7m or A$0.87 per basic share. This increase is largely driven by the inclusion of the agitation indication in our models. We assign a 20% probability of success for the programme given the limited data on BNC210 and the difficulty in developing a drug for this particular indication. We assume that the company will be able to bring the drug to market in FY23 following a 320-person Phase III. We model peak penetration of 10% into the market of institutionalized dementia patients with aggression in Europe and the US.
Our valuation is additionally increased by advancing our NPVs to the most recent period. We expect to update our valuation with the release of data from the ongoing PTSD study in calendar H218. We may add indications at this time if the results are suggestive of broader applications. The company has completed the Phase I clinical study of BNC101 in colorectal cancer (CRC). The company previously stated at an interim update that no safety issues were observed, and it provided an update in a poster presentation at the AACR 2018 meeting that no biomarkers of gut toxicity were observed. However, it has not released detailed results from the trial. We expect to update our valuation following the release of these data.
Exhibit 3: Valuation of Bionomics
Programme |
Market |
Prob. of success |
Launch year |
Peak sales (A$m) |
Margin/ Royalty |
rNPV (A$m) |
BNC210 |
PTSD |
30% |
2022 |
916.3 |
54% |
349.7 |
BNC210 |
Agitation |
20% |
2023 |
259.0 |
52% |
47.6 |
BNC101 |
CRC |
10% |
2025 |
1103.3 |
55% |
80.2 |
Merck collaboration milestones |
Alzheimer's associated cognitive dysfunction |
10% |
2025 |
1821.0 |
5% |
17.1 |
CRO business |
6.6 |
4% |
1.3 |
|||
Unallocated costs |
(16.7) |
|||||
Total |
|
|
|
|
|
$479.2 |
Net cash and equivalents (FQ318) (A$m) |
$12.9 |
|||||
Total firm value (A$m) |
$492.1 |
|||||
Total shares (m) |
482.8 |
|||||
Value per share (A$) |
$1.02 |
|||||
Dilutive warrants and options (m) |
52.34 |
|||||
Total diluted shares |
535.1 |
|||||
Value per diluted share (A$) |
0.97 |
|||||
Source: Edison Investment research, Bionomics reports
Financials
The company recently provided an update on cash flows for fiscal Q318. Operational cashflow was roughly breakeven for the period following the receipt of A$8.1m in government incentive payments, leaving the company’s cash balance largely unchanged at A$32.2m. Debt also remained steady at A$19.4m. Our forecasts remain largely unchanged at this time. We record the company’s future financing shortfall as A$35m in illustrated debt in FY20, although these needs can potentially be met through licensing activity.
Exhibit 4: Financial summary
$'000 |
2015 |
2016 |
2017 |
2018e |
2019e |
||
30-June |
IFRS |
IFRS |
IFRS |
IFRS |
IFRS |
||
INCOME STATEMENT |
|||||||
Revenue |
|
|
6,827 |
8,143 |
18,606 |
17,500 |
5,100 |
Cost of Sales |
0 |
0 |
0 |
0 |
0 |
||
Gross Profit |
6,827 |
8,143 |
18,606 |
17,500 |
5,100 |
||
EBITDA |
|
|
(15,665) |
(15,449) |
(3,214) |
(6,005) |
(27,140) |
Normalised operating profit |
|
|
(16,176) |
(16,071) |
(3,671) |
(6,461) |
(27,596) |
Amortisation of acquired intangibles |
(1,203) |
(1,316) |
(1,286) |
(1,286) |
(1,286) |
||
Exceptionals |
532 |
1,131 |
0 |
0 |
0 |
||
Share-based payments |
(515) |
(400) |
(504) |
(504) |
(504) |
||
Reported operating profit |
(17,362) |
(16,656) |
(5,461) |
(8,251) |
(29,386) |
||
Net Interest |
85 |
(668) |
(766) |
(677) |
(813) |
||
Joint ventures & associates (post tax) |
0 |
0 |
0 |
0 |
0 |
||
Exceptionals |
0 |
0 |
0 |
0 |
0 |
||
Profit Before Tax (norm) |
|
|
(16,091) |
(16,738) |
(4,437) |
(7,138) |
(28,409) |
Profit Before Tax (reported) |
|
|
(17,277) |
(17,324) |
(6,227) |
(8,928) |
(30,199) |
Reported tax |
328 |
732 |
(523) |
1,920 |
1,275 |
||
Profit After Tax (norm) |
(15,786) |
(16,031) |
(4,810) |
(5,603) |
(27,209) |
||
Profit After Tax (reported) |
(16,949) |
(16,592) |
(6,750) |
(7,008) |
(28,923) |
||
Minority interests |
0 |
0 |
0 |
0 |
0 |
||
Other comprehensive income |
3,313 |
968 |
(114) |
0 |
0 |
||
Net income (normalised) |
(12,473) |
(15,063) |
(4,924) |
(5,603) |
(27,209) |
||
Net income (reported) |
(13,637) |
(15,624) |
(6,864) |
(7,008) |
(28,923) |
||
Basic average number of shares outstanding (m) |
418 |
457 |
481 |
505 |
531 |
||
EPS - basic normalised (c) |
|
|
(3.78) |
(3.51) |
(1.00) |
(1.11) |
(5.13) |
EPS - diluted normalised (c) |
|
|
(3.78) |
(3.48) |
(0.98) |
(1.08) |
(5.02) |
EPS - basic reported (c) |
|
|
(4.06) |
(3.63) |
(1.40) |
(1.39) |
(5.45) |
Dividend (c) |
0.00 |
0.00 |
0.00 |
0.00 |
0.00 |
||
BALANCE SHEET |
|||||||
Fixed Assets |
|
|
31,251 |
31,723 |
29,597 |
28,096 |
26,676 |
Intangible Assets |
27,416 |
28,504 |
26,595 |
25,229 |
23,943 |
||
Tangible Assets |
3,451 |
2,835 |
2,618 |
2,484 |
2,350 |
||
Investments & other |
384 |
384 |
384 |
384 |
384 |
||
Current Assets |
|
|
37,881 |
58,086 |
54,478 |
50,085 |
22,602 |
Stocks |
410 |
439 |
426 |
426 |
426 |
||
Debtors |
9,069 |
11,003 |
9,893 |
9,758 |
9,825 |
||
Cash & cash equivalents |
26,558 |
45,450 |
42,874 |
38,615 |
11,066 |
||
Other |
1,844 |
1,194 |
1,286 |
1,286 |
1,286 |
||
Current Liabilities |
|
|
(13,706) |
(11,386) |
(13,889) |
(6,885) |
(8,431) |
Creditors |
(6,466) |
(5,855) |
(3,673) |
(5,231) |
(6,777) |
||
Tax and social security |
0 |
0 |
0 |
0 |
0 |
||
Short term borrowings |
(5,460) |
(2,732) |
(8,496) |
0 |
0 |
||
Other |
(1,780) |
(2,799) |
(1,720) |
(1,654) |
(1,654) |
||
Long Term Liabilities |
|
|
(23,460) |
(34,260) |
(29,733) |
(37,089) |
(35,060) |
Long term borrowings |
(9,317) |
(18,437) |
(10,014) |
(19,365) |
(19,365) |
||
Other long term liabilities |
(14,143) |
(15,824) |
(19,719) |
(17,724) |
(15,695) |
||
Net Assets |
|
|
31,966 |
44,163 |
40,454 |
34,208 |
5,788 |
Minority interests |
0 |
0 |
0 |
0 |
0 |
||
Shareholders' equity |
|
|
31,966 |
44,163 |
40,454 |
34,208 |
5,788 |
CASH FLOW |
|||||||
Op Cash Flow before WC and tax |
(15,665) |
(15,449) |
(3,214) |
(6,005) |
(27,140) |
||
Working capital |
17,290 |
(327) |
51 |
1,408 |
2,145 |
||
Exceptional & other |
3,310 |
417 |
1,723 |
(1,657) |
(3,343) |
||
Tax |
0 |
0 |
0 |
0 |
0 |
||
Net operating cash flow |
|
|
4,936 |
(15,360) |
(1,440) |
(6,254) |
(28,337) |
Capex |
(846) |
(197) |
(248) |
(323) |
(323) |
||
Acquisitions/disposals |
(391) |
69 |
0 |
0 |
0 |
||
Net interest |
941 |
1,232 |
1,201 |
1,204 |
1,111 |
||
Equity financing |
269 |
28,222 |
144 |
283 |
0 |
||
Dividends |
0 |
0 |
0 |
0 |
0 |
||
Other |
0 |
0 |
0 |
0 |
0 |
||
Net Cash Flow |
4,908 |
13,967 |
(342) |
(5,090) |
(27,549) |
||
Opening net debt/(cash) |
|
|
(6,856) |
(11,781) |
(24,281) |
(24,364) |
(19,250) |
FX |
17 |
(9) |
(10) |
(24) |
0 |
||
Other non-cash movements |
0 |
(1,457) |
435 |
0 |
0 |
||
Closing net debt/(cash) |
|
|
(11,781) |
(24,281) |
(24,364) |
(19,250) |
8,299 |
Source: Edison Investment research, Bionomics reports
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