Nova Challenge Biotech Business Contest / BDP Corporate Business Plan / Thomas J.

Hwang

Bio-Development Pharmaceuticals, Corp. (BDP)

Corporate Business Plan
I. INTRODUCTION

According to the World Health Organization’s (WHO) Expert Committee on Tropical Diseases,

onchocerciasis is the world’s third leading infectious cause of blindness, affecting nearly 20 million

people, primarily in remote areas of Africa (in over thirty countries), the Middle East (Yemen) and

Americas (Guatemala, Mexico, and Ecuador among others).1 Onchocerciasis is also known as river

blindness because the primary symptomatic condition is blindness induced by severe infection from

the parasitic microscopic worm (microfilariae) onchocerca volvulus and because many of the epidemic

loci are at or near rivers or rapidly flowing streams. The most common form of transmission of the

parasite is through the bite of an infected blackfly of the Simulium species, upon which the worms

subsequently spread rapidly throughout the body. The death of the worms, which can live and

perpetuate for up to fifteen years, triggers an immune system response, resulting in the destruction of

neighboring tissue, such as the eye. An estimated 300,000 to 500,000 have been irreversibly blinded by

onchocerciasis and even more forced to suffer from visual impairment.2 Onchocerciasis is infectious

and spreads from person to person through the blackfly intermediary – that is, blackflies that bite

humans infected with the disease can pass along the microfilariae to others. This infection mechanism

is particularly dangerous, as microfilariae cycle from human to blackfly to human again, such that

multiple bites sustained by an individual will radically increase the disease’s severity.

Generally classified as a neglected tropical disease, onchocerciasis is endemic in the developing

world, with 99% of all cases found on the African continent.3 It is the mission of Bio-Development

Pharmaceuticals, Corp. (BDP) to serve as the private sector leader in the eradication of the disease as

well as liaison and consultant for the multitude of existing actors in international public health

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programs. Indeed, the goals of the company are illustrated in our name: the innovative use of

biotechnological progress to drive sustainable economic, political and social development. Thus, the

work of BDP does not end in the development and distribution of a “cure”; rather, BDP also seeks to

introduce affected citizens to proper sanitation, water purification and health techniques that also

reduce the frequency of onchocerciasis and other tropical diseases. The founding core of BDP is not a

single medication; it is the guiding vision of improving the livelihoods of millions of poor and

vulnerable populations.

Our corporate philosophy can be summarized in the following motto: Innovation, Compassion

and Vision. BDP seeks to challenge the stereotype that socially-oriented companies cannot also be

economically profitable. Projected earnings models state that investors can expect nearly 10% more

from companies with stated and demonstrated commitments to society and the environment than their

counterparts. Finally, BDP has the potential to achieve more than traditional public-sector, not-for-

profit or governmental-based organizations by (1) developing the most cost-efficient medication and

streamlined production process by drawing from the benefits of the free market and (2) laterally

collaborating with other private-sector actors, mainly pharmaceutical companies.

II. SCIENTIFIC MECHANISM

Scientists thus far have discovered the mechanism by which onchocerca volvulus spreads from

the blackfly to the human body. First, the black fly, almost always female, ingests the parasite from the

dermis of another infected organism through what is known as a “blood meal.”4 The microfilariae

mature and eventually migrate to the thoracic muscles in the fly’s wings and finally, to the proboscis

and saliva.5 Through the bite wound, the parasites from the fly’s saliva enter the human circulatory

system vis-à-vis the blood stream. The larvae form nodules in the subcutaneous tissue, mature into

adult worms, and them release up to 1000 microfilariae per day. Dying microfilariae release

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Wolbachia-derived antigens, which trigger strong immune system responses and induce inflammation.6

Humans are the only known host of onchocerca volvulus, though the potential for mutation remains

open.

A variety of medical conditions are caused by contraction of onchocerciasis. The normal incubation

period of onchocerciasis ranges from nine to twenty four months after the first bite. A small percentage

of affected individuals report no initial symptoms. From this point the infection may be manifested in

dermatitis, skin rash, eye lesions, subcutaneous nodules under the skin, intense itching, and pain or

disfigurement. Dermatitis ranges from acute popular dermatitis, caused by scattered pruritic papules, to

total skin atrophy and depigmentation. In the most severe cases, the lesions in the eye progress into

blindness as the microfiliare migrate to the cornea of the eye. The initial punctate keratitis, which may

clear up if inflammation subsides, can degenerate into sclerosing keratitis. While the disease

disproportionately impacts residents of developing countries, onchocerciasis is also a risk for travelers

who stay in affected regions for prolonged periods of time, such as missionaries and volunteers.7

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In part due to the World Health Organization’s disease control

programs, the incidence of onchocerciasis has dropped

significantly. The Onchocerciasis Control Programme (OCP) was

launched in 1974, as a joint effort of the WHO, World Bank, United

Nations Development Programme (UNDP), and the Food and

Agriculture Organization (FAO), covering nearly 30 million people

in eleven different countries. Disease transmission was controlled

through the larvicide spraying of fast flowing rivers. OCP activities

were terminated in 2002, deemed to be a success. In 1992, the Onchocerciasis Elimination Programme

for the Americas (OEPA) expanded the disease prevention initiative’s reach to Central and South

American countries that have begun showing signs of incidence and similarly, the African Programme

for Onchocerciasis Control (APOC) covered nineteen more countries.8 The most common treatment

program, employed by the WHO and these programs, governments and non-governmental

organizations, involves vector control and mass administration of ivermectin, an oral drug donated by

Merck & Co., Inc. (Merck) through the Mectizan Donation Program (MDP) since 1988.9 Chemically,

ivermectin is known as 22, 23-dihydroavermectin B1a + 22, 23-dihydroavermectin B1b.Ivermectin

paralyzes the microfilariae, prevents them from reproducing and also prevents the dying worms to

cause the itching symptoms. The drug therefore prevents both “morbidity and transmission.”

Superficial skin biopsies (known as “snips”) are used to microscopically identify the parasites and,

because of the occasional false positive result, serologic testing of antibodies is also used. The oral

ivermectin dosage is generally approximately 150 micrograms per kilogram, a maximum of 12 mg,

during a time frame of six to twelve months.

While there is currently no known vaccine, preventative drug or chemoprophylaxis available,

ivermectin has substantially depressed onchocerciasis prevalence levels. However, based on recent

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discoveries, it seems that the disease has a change to resurge. According to a study published in The

Lancet and also publicized in a BBC news article, the worm may be developing resistance to

ivermectin.10 The longitudinal study conducted in select communities in Ghana from 2000 to 2005

showed that in spite of annual ivermectin treatments, the incidence of cases of infection doubled and

that “the ability of IVM [ivermectin] to suppress skin microfilariae repopulation was reduced in some

communities that had received 6-18 years of [the drug].”11 Genotyping studies have associated

resistance to ivermectin with genetic markers, particularly the β-tubulin gene in human onchocerca

volvulus. Sara Lustigman and James McCarter conclude in their paper:

The finding that IVM treatment selected for β-tubulin heterozygotes and that this selection was dependent on
dosage raises important concerns for the current river blindness control programs. These concerns are
heightened by the fact that this gene has been linked with IVM resistance in another parasitic nematode, and by
the recent evidence that IVM resistance is occurring in O. volvulus. Semiannual or more frequent treatments are
ongoing in some endemic areas and are under consideration in other areas. Such treatment might increase the
selection pressure. Therefore, Bourguinat and colleagues’ study is a wake-up call for control programs to select
their treatment regimens carefully and to develop plans for detecting IVM resistance and the associated genetic
markers (control programs will require additional funding for these plans). This study presents a possible
structure of study design that will incorporate the detection and validation of the genetic markers associated with
IVM resistance.12

Given the frightening prospect of ivermectin-resistant parasites, Bio-Development Pharmaceuticals

(BDP) proposes the following tripartite treatment program available to local and municipal authorities

as well as national governments.

Component 1: Enhanced Antiparasitic Regimens (EAR)

Instead of solely using ivermectin in the first line of attack against onchocerciasis, particularly

in newly affected regions, BDP recommends a treatment regimen that

proportionally relies on ivermectin and its complementary

macrofilaricide, doxycycline. A tetracycline antibiotic, doxycycline

has many clinical applications and is most famously used in

prophylaxis against malaria, anthrax and Yersinia pestis (the

infectious agent of bubonic plague). Adjunct treatment has been shown to “significantly lower

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microfilarial loads in the host and may have activity against the adult worms”13 because doxycycline

kills the endosybiotic Wolbachia bacteria and, therefore, also the nematodes. Ivermectin alone does not

kill the adult parasites but instead “reduces the numbers of microfilariae in the skin so the disease does

not progress.”14

Component 2: Accessible and Affordable Vaccine Candidates (AAVC)

The aforementioned macrofilaricide cocktail must be supplemented with a vaccine to ensure

long-term sustainability of disease eradication. Following the model of the International Vaccine

Institute, BDP will collaborate with non-profit and for-profit organizations in the development of an

anti-onchocerca vaccine. Substantial progress has been made in the development of the vaccine, with

the isolation of several expression vectors, in particular pOVEX, which combines the “advantages of

the expression vectors pGEX-3X and pJC2o” and “produces a fusion protein with the 24 kd

Onchocerca volvulus glutathione S-transferase (OvGST2) which is easy to purify in one step from

bacterial extracts under non-denaturing conditions using glutathione-sepharose chromatography.”15

pOVEX is of interest, in addition, because of its role in the production of parasitic antigens for the

“analyses of host humoural and cellular responses to these proteins and for immunization studies.”16

Component 3: Public Health Policy Consulting Services (PHPCS)

As mentioned previously, the mission of the BDP extends beyond the creation of a single

vaccine. Rather, BDP also anticipates a secondary role as a consultant to national governments and

ministries of health in the dissemination of public health information and in the development of

efficacious and appropriate campaigns to eradicate onchocerciasis that include best-practices

recommendations. These advisory notifications could range from wearing long-sleeve attire during

peak seasons of infection to timetables of insecticide spraying in localities. BDP, in consultation with

the World Health Organization, is also prepared to work with governments in surveying heavily-

affected regions for key focal points of treatment regimen-targeting.

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III. CORPORATE STRUCTURE

BDP is a for-profit organization governed by a Board of Directors, on which the President and

Chief Executive Officer (CEO) serves as Chair. Under the Board of Directors is the Scientific Steering

Committee, composed of internal and external scientific focal points and managers of specific focus

areas within the corporation (i.e. doxycycline manufacture, vaccine clinical trials, etc.). The Chair of

the Scientific Steering Committee will also sit on the Board of Directors and will be responsible for

overseeing the scientific, pharmaceutical and strategic management of the company.

Given the nature of the company’s work, mission and scope, BDP will collaborate extensively with

both private and public organizations. In particular, BDP will coordinate its activities organized under

the following thematic areas:

1. Pharmaceutical and Immunization Efforts – Merck & Co. (ivermectin), Pfizer, Inc.
(doxycycline), Food and Drug Administration (FDA), Bill and Melinda Gates Foundation,
Carter Center

2. Public Health Consulting – World Health Organization (WHO), World Bank, United Nations
Development Programme (UNDP), UN Food and Agriculture Organization (FAO), UNICEF,
USAID, Centers for Disease Control and Prevention (CDC), Non-governmental organizations

This interconnectivity naturally calls for hires to be made from several collaborating institutions. More

specifically, a tentative hiring schedule of selected positions would be as follows:

Position Preferred Previous Experience Starting Base Salary†

High level lateral recruit from biopharm
Chief Executive Officer company. Preferably with MD and MBA, or $500,000
equivalent medical and business experience.
Chair of the Scientific Steering Top academic scholar in international public
$200,000
Committee health and neglected tropical diseases
CDC, International Vaccine Institute,
Vice President of Vaccine similar institutions, preferably with
$150,000
Development experience in critical vaccines (such as
HIV/AIDS)
Vice President of Health Policy
World Health Organization $125,000
and Strategy

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Vice President of Marketing Merck, Pfizer, Bayer, Novartis $100,000

Director of Clinical Trials Academic pharmaceutical background $90,000
Vice President of Grants and
Gates Foundation $75,000
Major Gifts
Manager of Governmental UN agency or experience in an African
$60,000
Relations country’s Ministry of Health
† Starting base salaries do not include bonuses, restricted stock awards, common stock incentives, retirement
savings and other (i.e. health and pregnancy) benefits

BDP will operate two offices that reflect the company’s focus and interests. The primary

corporate office will be in New York City with research and development outsourced to nearby locales

in the tri-state metropolitan area, close to prominent research institutions and universities. Company

strategy and corporate management will originate from BDP’s headquarters in the United States. BDP

will also be housed in an office in Abuja, Nigeria from which all project implementation will be made

and contact with regional governments to monitor the progression of specific campaigns. Abuja was

selected for the second BDP office because it currently is the hub of United Nations activity in Nigeria

and Central Africa (regions heavily affected by river blindness) and also because 99% of all river

blindness cases are in Africa. The WHO, World Bank, USAID, UNICEF, UNAIDS, and the Nigerian

Ministry of Health have offices in Abuja. Proximity to these organizations will certainly facilitate

increased cooperation.

IV. ECONOMIC AND SOCIAL PROFITABILITY

Expected expenditures will inevitably cause investors to question how BDP can be profitable,

both economically and socially. BDP requires a unique corporate structure that yields maximal results

to shareholders and citizens of the world alike. Pursuant to the Bayh-Doyle Act, biotech start-up

companies, many of them small and founded by university researchers, carry out the initial clinical

phases of drug development. They then sign contracts with established big pharmaceutical companies,

effectively exchanging research for marketing. When a patent held by the biotech company is

eventually licensed to a pharmaceutical company, both are able to profit from the mutually symbiotic

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venture. This model is revised for BDP because (1) customers of BDP’s products in river blindness

cannot afford traditional alternatives and (2) social marketing is shared by national governments

(through public health campaigns). Thus, to maximize cost-effectiveness, BDP will hold a diversified

portfolio of drugs, products and consulting services for varied diseases. Some of these will be for

customers in the Western World, specifically the United States, and will therefore reflect the prices of

typical prescription drugs.

Even in its onchocerciasis operations, BDP’s innovative corporate structure minimizes

unnecessary costs. The goal of BDP in its efforts against onchocerciasis is to be profit-neutral. Profit-

neutral status (or “non-profit”) in this segment of the portfolio will also enable us to make a case for

grant applications, with the assistance of the company’s General Legal Counsel. First, the Vice

President of Grants and Major Gifts will be charged with procuring an initial pool of funds for basic

R&D as well as covering administrative costs from the vast array of grant-giving organizations in the

field of public health. The initial-public offering (IPO) will also contribute to this general capital pool,

to be tapped for catalyzing the company’s activities. Second, the Director of Clinical Trials will partner

with pharmaceutical companies and academic institutions in the development of the treatment regime

and the vaccine. BDP will in essence design the study and outsource the day-to-day clinical operations

to partner organizations, utilizing the same model as public-private partnerships such as the Global

Alliance for Tuberculosis Drug Development. Third, as mentioned previously, the burden of marketing

will be shared by national governments, BDP, and pharmaceutical partners. The Vice President of

Marketing will have the responsibility, therefore, of being the liaison between corporate partners and

their respective marketing teams and the management of BDP.

The most important benefit is the reputation gained by successfully leading the global fight

against a disease. Such publicity, as well as deepened trust from governments and intergovernmental

agencies, will ensure that profit-positive ventures (typically, patented drugs in the West) generate
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sufficient capital for corporate sustainability and shareholder satisfaction. Social profitability must, of

course, not be forgotten. It must be noted that with only $100, we will be able to prevent 2.5-14 years

of blindness, an additional 3.5-20 years of irritating skin disease and 3-17 years of impaired vision.

Onchocerciasis is a preventable disease that has been ignored for too long and with waning public

interest, the risk of traditional drug-resistant strains of the parasite looms on the horizon. It is BDP’s

mission to eradicate river blindness and restore vision and life to the afflicted throughout the world.

WORKS CITED

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1
World Health Organization, Onchocerciasis (WHO Control of Neglected Tropical Diseases, 2009) Accessed from:
<http://www.who.int/topics/onchocerciasis/en/>
2
Sightsavers International, What is River Blindness (2008) Accessed from: <http://www.sightsavers.org/What We Do/Eye
Conditions/River Blindness/World1622.html>
3
World Health Organization, Onchocerciasis.
4
World Bank, Global Partnership to Eliminate Riverblindness: The Disease (2007) Accessed from:
<http://www.worldbank.org/afr/gper/disease.htm>
5
World Health Organization, Life Cycle of Onchocerciasis (African Programme for Onchocerciasis Control, 2008)
Accessed from: < http://www.who.int/apoc/onchocerciasis/lifecycle/en/index.html>
6
Ibid.
7
James, William D., Timothy G. Berger, et al, Andrew’s Diseases of the Skin: Clinical Dermatology (Saunders Elsevier,
2006)
8
World Health Organization, African Programme for Onchocerciasis Control (2008) Accessed from
<http://www.who.int/apoc/en/index.html>
9
African Programme for Onchocerciasis Control, Community-directed Treatment.
10
BBC News, “River blindness resistance fears” (2007) Accessed from: <http://news.bbc.co.uk/2/hi/health/6753003.stm>
11
Lustigman, Sara and James P. McCarter, “Ivermectin Resistance in Onchocerca volvulus: Toward a Genetic Basis”. PLoS
Negl Trop Dis. 2007 October; 1(1): e76.
12
Ibid.
13
Taylor MJ, Bandi C and Hoerauf A, “Wolbachia bacterial endosymbionts of filarial nematodes” (Adv. Parasitol., 2005)
60:245-84. Accessed from <http://linkinghub.elsevier.com/retrieve/pii/S0065-308X(05)60004-8>
14
CDC Division of Parasitic Diseases, River Blindness (Onchocerciasis) (2007) Accessed from:
<http://www.cdc.gov/ncidod/dpd/parasites/onchocerciasis/factsht_onchocerciasis.htm>
15
Liebau, Eva, Spillner E, Henkle-Duhrsen K, “pOVEX vector: prokaryotic expression and purification of onchocerciasis
vaccine candidate antigens as fusion proteins with the 24 kD Onchocerca volvulus glutathione S-transferase.” Tropical
Medicine & International Health. 2(7):691-694, July 1997.
16
Ibid.