Speaker Program

Supported by DARA BioSciences Inc., Leaders in Oncology Supportive Care

The Benefits of Soltamox® (tamoxifen citrate) Oral Solution in Breast Cancer Patients

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Agenda

• Breast Cancer and the use of tamoxifen citrate

• Soltamox® (tamoxifen citrate) oral solution

• Improving Patient Outcomes

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DISCLAIMERS

 • This program was developed by DARA

BioSciences Inc. and I presenting on behalf of DARA BioSciences Inc.

• I have received compensation from DARA BioSciences Inc. to make this presentation.

• The information I am presenting is consistent with the full prescribing information for Soltamox® (tamoxifen citrate) oral solution as required under applicable Food and Drug regulations.

• Copies of the full prescribing information for Soltamox® (tamoxifen citrate) oral solution are available at this presentation and at www.Soltamox.com.

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Breast Cancer

US Prevalence*

– 2.6M women with a history of breast cancer

– ~290K new cases each year

• 230K invasive and 58K in-situ

Tamoxifen citrate**

– Used to treat estrogen receptor + breast cancer (~80% all cases), to reduce the risk of recurrence

– Prevention in high-risk patients

– Used in up to 40% of patients (~1.8 M Rx written per year)

– Treatment period up to 5 years

* American Cancer Society - Facts and Figures 2011-2012; ** Tamoxifen citrate US Package Insert; Symphony Rx data 2012

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Adjuvant Endocrine Therapy NCCN Guidelines (BINV-J)

NCCN Treatment Guidelines Version 3. 2013 (AI = Aromatase Inhibitor)

Pre-menopausal Tamoxifen 5 yrs Pre-

menopausal

Post-menopausal

Consider tamoxifen +5 yrs or No further endocrine treat.

Aromatase inhibitor 5 yrs

AI to complete 5 yrs or up to 5 yrs AI

Post-menopausal

AI contra-indicated

Tamoxifen4.5-6 yrs

AI 5 yrs or Tamoxifen 2-3 yrs orAI 2-3 yrs

Tamoxifen 5 yrs or consider tamoxifen up to 10 yrs

AI 5 yrs or consider tamoxifen for +5 yrs

Tamoxifen to complete 5 yrs

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Tamoxifen Efficacy - DCIS*

• NSABP B-24 Trial– Double-blind, randomized, placebo-controlled trial – 1,804 women randomized to tamoxifen 20mg/day

or placebo (in addition to lumpectomy and radiation)

– For the primary endpoint, the incidence of invasive breast cancer was reduced by 43% among women assigned to tamoxifen

– 44 cases tamoxifen vs. 74 cases placebo; p=0.004

*DCIS = Ductal Carcinoma in Situ; NSABP B-24 Trial (Tamoxifen citrate Package Insert)

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Tamoxifen - Breast Cancer Prevention

• Tamoxifen citrate is indicated to reduce the incidence of breast cancer in women at high risk for breast cancer*– Defined as women at least 35 years of age

with a 5-year predicted risk of breast cancer ≥ 1.67%, as calculated by the Gail Model

*Tamoxifen citrate Package Insert

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Tamoxifen Efficacy in High Risk Women

• NSABP P-1 Trial– Double-blind, randomized, placebo controlled

trial – 13,388 women at least 35 yrs, randomized to

tamoxifen 20mg/day or placebo for 5 yrs – After a median follow-up of 4.2 years, the

incidence of invasive breast cancer was reduced by 44%

– 86 cases tamoxifen vs. 156 cases placebo; p<0.00001

NSABP P-1 trial; Tamoxifen citrate Package Insert

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Soltamox® (tamoxifen citrate) Oral Solution

• Launched in the US, Nov. 2012– Bioequivalent to tamoxifen tablets– Same indications as tamoxifen tablets

• With free Co-pay assistance, same low monthly cost ($10) as generic tablets• Recommended dosage

– Tamoxifen 20-40mg per day– 20mg Soltamox = 10 mL

• Measuring cup supplied

Soltamox (tamoxifen citrate) oral solution Package Insert

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Offering Patients a Choice = Preference

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One pharmacokinetic study has been performed in healthy perimenopausal and postmenopausal female subjects to evaluate the bioavailability of Soltamox® in comparison with the commercially available tamoxifen citrate tablets under fasting condition and also to determine the drug absorption from Soltamox® under fed conditions. The rate and extent of absorption of Soltamox® was found to be comparable to that of tamoxifen citrate tablets under fasting condition as shown in the table.

Soltamox (tamoxifen citrate) oral solution Package Insert

Parameter

Soltamoxliquid

(n=30)Mean (SD)

Tamoxifen Citrate tablet(n=33)

Mean (SD)

AUC (ng.hr/mL) 4131.57 (1499.45) 4105.61 (1431.90)

AUCT (ng.hr/mL) 3108.82 (847.38) 3229.47 (900.86)

Cmax (ng/mL) 53.38 (14.03) 55.94 (13.63)

Tmax (hour) a 4.5 (2.13-8.00) 4.5 (3.0-8.0)

t½ (hour) 255.70 (69.58) 227.43 (58.88)

Soltamox®

Bioequivalent to Tamoxifen Tablets

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Soltamox® The Same Indications as tamoxifen

citrateMetastatic Breast Cancer Tamoxifen citrate is effective in the treatment of metastatic breast cancer in women and men.

Adjuvant Treatment of Breast Cancer Tamoxifen citrate is indicated for the treatment of node-positive breast cancer in postmenopausal women following total

mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. In some tamoxifen citrate adjuvant studies, most of the benefit to date has been in the subgroup with four or more positive axillary nodes.

Tamoxifen citrate is indicated for the treatment of axillary node-negative breast cancer in women following total mastectomy or segmental mastectomy, axillary dissection, and breast irradiation. The estrogen and progesterone receptor values may help to predict whether adjuvant tamoxifen citrate therapy is likely to be beneficial.

Tamoxifen citrate reduces the occurrence of contra lateral breast cancer in patients receiving adjuvant tamoxifen citrate therapy for breast cancer.

Ductal Carcinoma in Situ (DCIS) In women with DCIS, following breast surgery and radiation, tamoxifen citrate is indicated to reduce the risk of invasive breast

cancer (see BOXED WARNING at the beginning of the Prescribing Information). The decision regarding therapy with tamoxifen for the reduction in breast cancer incidence should be based upon an individual assessment of the benefits and risks of tamoxifen therapy.

Reduction in Breast Cancer Incidence in High Risk Women Tamoxifen citrate is indicated to reduce the incidence of breast cancer in women at high risk for breast cancer. (see BOXED

WARNING at the beginning of the Prescribing Information). Tamoxifen citrate is indicated only for high-risk women. "High risk" is defined as women at least 35 years of age with a 5-year predicted risk of breast cancer = 1.67%, as calculated by the Gail Model.

Dosage and administration For patients with breast cancer, the recommended daily dose is 20-40 mg. Dosages greater than 20 mg per day should be given

in divided doses (morning and evening). A 20 mg dose of SOLTAMOX™ is administered as 10 mL (equivalent to 2 teaspoons) of the oral solution (Please see the Full Prescribing Information for complete dosage instructions.)

Please see full Prescribing Information and complete Black Box Warning contained within your presentation folder.

Soltamox (tamoxifen citrate) oral solution Package Insert

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Serious and life-threatening events associated with tamoxifen medications such as Soltamox (tamoxifen citrate) in the risk reduction setting (women at high risk for cancer and women with DCIS) include uterine malignancies, stroke and pulmonary embolism. Some of the strokes, pulmonary emboli, and uterine malignancies were fatal. Health care providers should discuss the potential benefits versus the potential risks of these serious events with women at high risk of breast cancer and women with DCIS considering tamoxifen to reduce their risk of developing breast cancer. The benefits of tamoxifen outweigh its risks in women already diagnosed with breast cancer.

Soltamox® (tamoxifen citrate) oral solution

The Same Important Safety Information

Soltamox (tamoxifen citrate) oral solution Package Insert

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In Women with Ductal Carcinoma in Situ (DCIS) and Women at High Risk for Breast Cancer Serious and life-threatening events were associated with tamoxifen in the risk reduction setting (women at high risk for cancer and women with DCIS) include uterine malignancies, stroke and pulmonary embolism. (see CLINICAL PHARMACOLOGY, Clinical Studies, Reduction in Breast Cancer Incidence In High Risk Women).  Health care providers should discuss the potential benefits versus the potential risks of these serious events with women at high risk of breast cancer and women with DCIS considering tamoxifen to reduce their risk of developing breast cancer. The benefits of tamoxifen outweigh its risks in women already diagnosed with breast cancer.

Soltamox® (tamoxifen citrate) oral solution

The Same Black Box Warning

Soltamox (tamoxifen citrate) oral solution Package Insert

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Improving Patient Outcomes

• Important considerations:– Patient preference– Long term adherence

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Preference – The Importance of Offering Patients a Choice

• Some patients prefer a liquid to tablets/pills– Psychological factors, anxiety

• Can address/identify underlying pathologies– Age related swallowing difficulties– Co-existing conditions (e.g. neurological, acid-reflux) – Effect of other medications (e.g. that cause dry mouth, have anticholinergic or CNS-depressing effects)

• Consistent with good practices

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Consistent with Good Practices“The 8 Rights of Medication

Administration”

1. Right Patient2. Right Medication3. Right Dose4. Right Route

– check the order and appropriateness of the route ordered

– confirm that the patient can take or receive the medication by the ordered route

5. Right Time6. Right Documentation7. Right Reason8. Right Response

*Nursing Center.com May 27, 2011 Lisa Bonsall, MSN, RN, CRNP

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Good Administration Practices

• CMS* policies and procedures require the correct route, to ensure that the method of administration is the appropriate one for that particular medication and patient

• Standards for Medicines Management** recommend that dosage, method of administration, route and timing be considered during the administration of medicines

*CMS Guidance on Medication Administration, Hospital Appendix A P.10 (2011) **Standards for Medicines Management NMC pg.6 (UK)

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Underlying Pathologies

CONDITIONS e.g.

•Neurological disorders incl. stroke•Structural lesions•Connective tissue diseases•Iatrogenic causes

MEDICATIONS e.g.

•Cause dry mouth•Anticholinergic or antimuscarinic effects•Certain antipsychotic and neuroleptics•Depress the CNS

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Age Related -40% patients on tamoxifen

>65yrs

Patient Gender

Female = 99.9%

Male = 0.1%

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Source: Catalina Retail Pharmacy data base (N = 27,315 pts.)

Approx. 40% >65yrs

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Improving Patient Outcomes- Better Long Term Adherence

“We’re doing well with women taking endocrine therapy, but there’s work to do. If guidelines begin to shift so that some women at high risk of breast cancer recurring need 10 years of endocrine therapy, then the number of women who persist with treatment will likely worsen. We need better ways of supporting women through this therapy”

Christopher Friese. Assistant Professor, University of

Michigan School of Nursing*

• Lead study author, Adjuvant endocrine therapy initiation and persistence in a diverse sample of patients with breast cancer. Breast Cancer Res Treat. 2013 Friese C et al Apr;138(3):931-9. doi: 10.1007/s10549-013-2499-9

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Adherence – University of Michigan Study (2013)

• Study of 743 women eligible for endocrine therapy (tamoxifen or aromatase inhibitors)

• Women surveyed in Detroit and Los Angeles

• Reported to SEER (Surveillance, Epidemiology and End Results) registry– 11 % never initiated therapy– 15% stopped early

Breast Cancer Res Treat. 2013 Friese C et al Apr;138(3):931-9. doi: 10.1007/s10549-013-2499-9

26%

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University of Michigan Study

• The most common reason patients discontinue or never start therapy is side effects– menopause-like symptoms, joint pain

• Women who expressed more worry about cancer recurring were more likely to complete their endocrine therapy.

• Women who reported receiving less information about endocrine therapy were less likely to begin taking it.

Breast Cancer Res Treat. 2013 Friese C et al Apr;138(3):931-9. doi: 10.1007/s10549-013-2499-9

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Murphy et al Adherence to adjuvant hormonal therapy among breast cancer survivors in Clinical practice: a systematic review. Breast Cancer Research Treat Pub. Online 12 June 2012

Murphy C et al. Breast Cancer Research and Treatment 2012

Tamoxifen AdherenceA Systematic Review of 30 Studies

At the end of 5 years treatment:

• Adherence: 41% - 72%

• Discontinuation: 31% - 73%

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McCowan C et al. Cohort study examining tamoxifen adherence and its relationship to mortality in women with breast cancer British Journal of Cancer (2008) 99, 1763–1768. doi:10.1038/sj.bjc.6604758 www.bjcancer.com Published online 4 November 2008

McCowan et al. British Journal Cancer, 2008

Tamoxifen Adherence

“Patients who are prescribed adjuvant tamoxifen… have a lower risk of death”

“Cumulative non-persistence with tamoxifen therapy occurs in nearly half of patients….”

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Of 961 women ≥65 years prescribed tamoxifen,

49% discontinued treatment before 5 years.Cynthia Owusu et al. Predictors of Tamoxifen Discontinuation among Older Women with Estrogen Receptor–Positive Breast Cancer. Journal of Clinical Oncology. Volume 26 Number 4 549-555, February 1 2008

Tamoxifen Discontinuation Women ≥ 65 yrs

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US Tamoxifen Prescribers Believe Patients Have Adherence Issues

Patient adherence(Percentage of tamoxifen

prescribers)

4%

51%

42%

3%

never miss a dose

rarely miss a dose

sometimes miss a dose

frequently miss a dose

My patients on Tamoxifen…

55%

Yes

45%No

On average, respondents believe that 15% of their breast cancer

patients stop taking their Tamoxifen prior to the prescribed

duration

Patients with issues taking medication long-term as prescribed(Percentage of tamoxifen prescribers)

US Market Research (on-line) Gelclair and Soltamox; Conducted Jan 2013 N=103

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Reason Why Patients Stop Taking Tamoxifen

Reasons patients stop taking Tamoxifen

tablet therapy earlyPercentage of writers

28%

49%

54%

40%

68%

89%

86%

88%1%

98%

1%

34% 17%9%

9%Too expensive/can’t afford to pay for prescription

Lack of understanding regarding importance

16%

10%

12%Patient feels better and stops taking medication

12%

24%

25%

15%

Multiple conditions/pills - forget to take

Drug side effects

8%

51% 11% 11%

6%

6%

Lack of follow-up by primary care provider 3%

4%Have difficulty swallowing in general

5%Have difficulty swallowing tablets as a result of

chemotherapy or radiation therapy 4%

4%

2%Other

Not rankedRanked 2 Ranked 3Ranked 1

US On-line Market Research among oncologists and oncology nurses; Jan 2013 (N=103)

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Possible Ways to Improve Long Term Adherence to Tamoxifen

• Educate pts. regarding the importance of long term tamoxifen therapy

• Educate pts. regarding the management of tamoxifen side effects

• Monitor pt. adherence• Assess pts. ability to swallow• Offer pts. a choice of a liquid vs. a

tablet– Patients who have a say in their “choice” of

medicine may be more compliant on a daily basis

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Do you prefer a liquid

medication or pills?

How do you take your tablets?

Do you use applesauce or crush them?

Do you think taking a liquid form of tamoxifen will help you take your therapyover the long term?

Simple Questions

Do you take your tamoxifen tabletsevery day?

Do you find itdifficult to swallow certain things?

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Summary - Patients Who May Benefit From Soltamox

Tamoxifen Patients who prefer a liquid vs. a pill

Patients who have underlying “pathology” (e.g., cancer treatment, co-existing

disease, concomitant meds, physical or psychological issues)

Patients with tablet adherence issues who

may benefit from a change

Offering patientsa choice

between a pill and asolution may

support long termadherence.

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Conclusions

• Tamoxifen has proven efficacy, yet treatment remains sub-optimal due to poor adherence

• Two dose forms (tablets, liquid) are now available– Soltamox has the same indications and is

bioequivalent to tamoxifen citrate tablets

• Offering patients a choice may improve adherence• Patients who have a say in their “choice” of

medicine may be more compliant on a daily basis

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Discussion Topics

• To what extent do your breast cancer patients have adherence issues with tamoxifen?– Main reasons?– Impact on treatment outcomes?– Ways to monitor?– Ways to address?

• Does it make sense to offer patients a choice between tablets and liquid tamoxifen?

• Do you see a role for Soltamox in certain populations?– Patient types?– How to keep Soltamox top-of-mind?